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Leisi Mehrabani F, Alibeigian Y, Baghaban Eslaminejad M, Hosseini S. Mechanical harvesting of cell sheets: an efficient approach for bone and cartilage tissue engineering. Stem Cell Res Ther 2025; 16:310. [PMID: 40528269 DOI: 10.1186/s13287-025-04411-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2025] [Accepted: 05/21/2025] [Indexed: 06/20/2025] Open
Abstract
Cell sheet engineering (CSE) has demonstrated significant promise for the advancement and application of tissue-engineered constructs in the fields of tissue engineering and regenerative medicine. In this technology, cells are cultured to form a monolayer, which is then detached from the culture surface as a complete sheet. This process preserves cell interactions, maintains cellular phenotypes and functions, and retains the integrity of the cell-extracellular matrix (ECM). A main characteristic of the cell sheet is its ability to retain the native ECM components secreted by cells. When the ECM is preserved in cell sheets, cells are surrounded by a much more biologically appropriate environment to increase their regenerative potential, thereby offering more native conditions for cell growth and differentiation. CSE has shown promising results in a wide range of applications, including bone and cartilage. The cell sheets can be directly transplanted to the target site, where they integrate with the host tissue and enhance regeneration. The main challenge in CSE is how to detach an intact cell sheet without disturbing the ECM and cell‒cell connections. There are various methods for removing cell sheets that lead to the harvesting of intact cell sheets. Among the various methods for harvesting cell sheets, temperature-responsive systems and mechanical peeling are the most common. Mechanical harvesting, in particular, is a simple, cost-effective, accessible method that is widely used in research, especially in the scope of bone and cartilage tissue engineering. This article aims to review the application of cell sheets in bone and cartilage tissue engineering, with a focus on practical and cost-effective mechanical harvesting methods.
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Affiliation(s)
- Fatemeh Leisi Mehrabani
- Faculty of Sciences and Advanced Technologies in Biology, University of Science and Culture, Tehran, Iran
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Yalda Alibeigian
- Faculty of Sciences and Advanced Technologies in Biology, University of Science and Culture, Tehran, Iran
| | - Mohamadreza Baghaban Eslaminejad
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
| | - Samaneh Hosseini
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
- Department of Cell Engineering, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
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Yu JL, Yang C, Liu L, Lin A, Guo SJ, Tian WD. Optimal good manufacturing practice-compliant production of dental follicle stem cell sheet and its application in Sprague-Dawley rat periodontitis. World J Stem Cells 2025; 17:104116. [DOI: 10.4252/wjsc.v17.i5.104116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Revised: 02/27/2025] [Accepted: 04/18/2025] [Indexed: 05/26/2025] Open
Abstract
BACKGROUND Dental follicle stem cell (DFSC) sheets demonstrate strong extracellular secretion capabilities and efficacy in periodontal regeneration. However, existing methods for producing DFSC sheets lack a comprehensive discussion on the most efficient and cost-effective approaches at the good manufacturing practice (GMP) level.
AIM To investigate the culture condition of GMP-compliant DFSC sheets and to compare the properties of DFSC sheets and cell suspensions.
METHODS This study explored the optimal conditions for culturing GMP-compliant DFSC sheets, focusing on four key factors: Cell passage, cell concentration, L-ascorbic acid content, and culture duration. We evaluated the characteristics of the cell sheets under varying culture conditions, including cell viability, cell count, appearance, osteogenesis, chondrogenesis, odontogenesis, aging, relative telomere length, and extracellular matrix secretion. A comparison was also made between the periodontal regeneration, osteogenesis, and paracrine capacity of cell sheets cultured under optimal conditions and those of the cell suspensions.
RESULTS The GMP-compliant DFSC sheets cultured from passage 4 cells exhibited the highest viability (≥ 99%, P < 0.05) and optimal osteogenic differentiation capacity (optical density ≥ 0.126, P < 0.05). When cultured for 10 days, DFSC sheets demonstrated maximal expression of osteogenic, chondrogenic and periostin genes [alkaline phosphatase, Runt-related transcription factor 2, collagen type I, osteopontin, cartilage associated protein, and PERIOSTN (P < 0.001); osteocalcin (P < 0.01)]. Concurrently, they showed the lowest senescent cell count (P < 0.01) with no progression to late-stage senescence. At a seeding density of 2500 cells/cm2, GMP-compliant DFSC sheets achieved better osteogenic differentiation (P < 0.01) and maximal osteogenic, chondrogenic and periostin gene expression (P < 0.001), coupled with the highest hydroxyproline secretion (P < 0.001) and moderate sulfated glycosaminoglycan production. No statistically significant difference in senescent cell count was observed compared to DFSC sheets at a seeding density of 5000 cells/cm2. Supplementation with 25 μg/mL L-ascorbic acid significantly enhanced osteogenic gene expression (P < 0.001) and elevated hydroxyproline (P < 0.01) and sulfated glycosaminoglycan secretion to high ranges. Compared with the cell suspension, the cell sheet demonstrated improved osteogenic, paracrine, and periodontal regenerative capacities in Sprague-Dawley rats. The optimized DFSC sheets demonstrated significantly higher levels of vascular endothelial growth factor and angiopoietin-1 (P < 0.001) compared to DFSC suspensions, along with enhanced osteogenic induction outcomes (optical density = 0.1333 ± 0.01270 vs 0.1007 ± 0.0005774 in suspensions, P < 0.05). Following implantation into the rat periodontal defect model, micro-computed tomography analysis revealed superior bone regeneration metrics in the cell sheet group compared to both the cell suspension group and control group (percent bone volume, trabecular thickness, trabecular number), while trabecular spacing exhibited an inverse pattern.
CONCLUSION Optimized DFSC sheets cultured under the identified conditions outperform DFSC suspensions. This study contributes to the industrial-scale production of DFSC sheets and establishes a foundation for cell therapy applications.
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Affiliation(s)
- Jia-Lu Yu
- State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Chao Yang
- Department of Product Development, Chengdu Shiliankangjian Biotechnology Co., Ltd, Chengdu 610041, Sichuan Province, China
| | - Li Liu
- Engineering Research Center of Oral Translational Medicine, National Clinical Research Center for Oral Diseases, Departments of 5 Periodontics and 6 Oral and Maxillofacial Surgery, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - An Lin
- State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Shu-Juan Guo
- Department of Periodontics, West China School of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Wei-Dong Tian
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Engineering Research Center of Oral Translational Medicine, National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
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Jin L, Hwang B, Rezapourdamanab S, Sridhar V, Nandwani R, Amoli MS, Serpooshan V. Bioengineering Approaches to In Vitro Modeling of Genetic and Acquired Cardiac Diseases. Curr Cardiol Rep 2025; 27:72. [PMID: 40111543 PMCID: PMC11926001 DOI: 10.1007/s11886-025-02218-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/13/2025] [Indexed: 03/22/2025]
Abstract
PURPOSE OF REVIEW This review aims to explore recent advancements in bioengineering approaches used in developing and testing in vitro cardiac disease models. It seeks to find out how these tools can address the limitations of traditional in vitro models and be applied to improve our understanding of cardiac disease mechanisms, facilitate preclinical drug screening, and equip the development of personalized therapeutics. RECENT FINDINGS Human induced pluripotent stem cells have enabled the generation of diverse cardiac cell types and patient-specific models. Techniques like 3D tissue engineering, heart-on-a-chip platforms, biomechanical conditioning, and CRISPR-based gene editing have enabled faithful recreation of complex cardiac microenvironments and disease conditions. These models have advanced the study of both genetic and acquired cardiac disorders. Bioengineered in vitro models are transforming the basic science and clinical research in cardiovascular disease by improving the biomimicry and complexity of tissue analogues, increasing throughput and reproducibility of screening platforms, as well as offering patient and disease specificity. Despite challenges in scalability and functional maturity, integrating multiple bioengineering techniques with advanced analytical tools in in vitro modeling platforms holds promise for future precision and personalized medicine and therapeutic innovations.
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Affiliation(s)
- Linqi Jin
- Department of Biomedical Engineering, Emory University School of Medicine and Georgia Institute of Technology, Atlanta, GA, 30322, USA
| | - Boeun Hwang
- Department of Biomedical Engineering, Emory University School of Medicine and Georgia Institute of Technology, Atlanta, GA, 30322, USA
| | - Sarah Rezapourdamanab
- Department of Biomedical Engineering, Emory University School of Medicine and Georgia Institute of Technology, Atlanta, GA, 30322, USA
| | - Vani Sridhar
- Department of Biomedical Engineering, Emory University School of Medicine and Georgia Institute of Technology, Atlanta, GA, 30322, USA
| | - Roshni Nandwani
- Department of Biology, Emory University, Atlanta, GA, 30322, USA
| | - Mehdi Salar Amoli
- Department of Biomedical Engineering, Emory University School of Medicine and Georgia Institute of Technology, Atlanta, GA, 30322, USA
| | - Vahid Serpooshan
- Department of Biomedical Engineering, Emory University School of Medicine and Georgia Institute of Technology, Atlanta, GA, 30322, USA.
- Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, 30322, USA.
- Children's Healthcare of Atlanta, 1075 Haygood Dr., Suite N425, Atlanta, GA, 30322, USA.
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Li YL, Chen EG, Ren BB. Umbilical cord-derived mesenchymal stromal cells: Promising therapy for heart failure. World J Cardiol 2025; 17:101153. [PMID: 39866217 PMCID: PMC11755126 DOI: 10.4330/wjc.v17.i1.101153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Revised: 11/06/2024] [Accepted: 12/02/2024] [Indexed: 01/21/2025] Open
Abstract
Heart failure (HF) is a complex syndrome characterized by the reduced capacity of the heart to adequately fill or eject blood. Currently, HF remains a leading cause of morbidity and mortality worldwide, imposing a substantial burden on global healthcare systems. Recent advancements have highlighted the therapeutic potential of mesenchymal stromal cells (MSCs) in managing HF. Notably, umbilical cord-derived MSCs (UC-MSCs) have demonstrated superior clinical potential compared to traditional bone marrow-derived MSCs; this is evident in their non-invasive collection process, higher proliferation efficacy, and lower immunogenicity and tumorigenicity, as substantiated by preclinical studies. Although the feasibility and safety of UC-MSCs have been tested in animal models, the application of UC-MSCs in HF treatment remains challenged by issues such as inaccurate targeted migration and low survival rates of UC-MSCs. Therefore, further research and clinical trials are imperative to advance the clinical application of UC-MSCs.
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Affiliation(s)
- Ya-Lun Li
- Department of Pulmonary and Critical Care Medicine, Regional Medical Center for National Institute of Respiratory Disease, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
- Medical College, Zhejiang University, Hangzhou 310063, Zhejiang Province, China
| | - En-Guo Chen
- Department of Pulmonary and Critical Care Medicine, Regional Medical Center for National Institute of Respiratory Disease, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
| | - Bing-Bing Ren
- Department of Pulmonary and Critical Care Medicine, Regional Medical Center for National Institute of Respiratory Disease, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, Zhejiang Province, China.
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Zangiabadi I, Askaripour M, Rajizadeh MA, Badreh F, Bagheri MM, Jafari E, Shamsara A, Shafiei G, Rajabi S. Conditioned medium from human adipose-derived mesenchymal stem cells attenuates cardiac injury induced by Movento in male rats: role of oxidative stress and inflammation. BMC Pharmacol Toxicol 2025; 26:13. [PMID: 39844289 PMCID: PMC11753139 DOI: 10.1186/s40360-025-00847-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Accepted: 01/17/2025] [Indexed: 01/24/2025] Open
Abstract
Movento an insecticide containing spirotetramat, has been shown to cause severe toxicity in humans and rats. Due to the widespread use of the Movento in agriculture, and since the cardiac effects of this toxin have not been investigated in any study so far, in this study, for the first time, the effect of movento on the structure and function of the heart in rats was investigated. 24 adults' male Wistar rats randomly divided to 4 experimental groups: 1- control (CTL), 2- Movento (M) 3- M + Basal media (BM) 4- M + Conditioned medium (CM). Animals were subjected to deep anesthesia to record the ECG and blood pressure. H&E staining was performed to determine the degree of damage. Oxidative stress markers and inflammatory factors were investigated with related kits. In rats that received Movento's insecticide, mean arterial pressure (MAP), amplitude of the P wave and total antioxidant capacity (TAC) decreased compared to the control group and treatment with CM increased them significantly compared to M and M + BM group. Also, Movento increased histological score, MDA, TNF-α and IL-6 compared to the control group and CM significantly decreased them compared to M and M + BM groups. CM derived from mesenchymal stem cells (MSC) can be used as a therapy for heart disorders caused by movento toxin in the heart of rats. Also, it seems that this treatment could be a promising way to improve heart complications in farmers exposed to this toxin in the future.
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Affiliation(s)
- Iman Zangiabadi
- Department of Basic Sciences, School of Medicine, Bam University of Medical Sciences, Bam, Iran
- Department of anatomy, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Majid Askaripour
- Department of Physiology, School of Medicine, Bam University of Medical Sciences, Bam, Iran
| | - Mohammad Amin Rajizadeh
- Endocrinology and Metabolism Research Center, Kerman University of Medical Sciences, Kerman, Iran
- Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Jehad Blvd, Ebn Sina Avenue, Kerman, 76198-13159, Iran
| | | | - Mohammad Mehdi Bagheri
- Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
| | - Elham Jafari
- Pathology and Stem Cell Research Center, Department of Pathology, Kerman University of Medical Sciences, Kerman, Iran
| | - Ali Shamsara
- Department of anatomy, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
- Institute of Neuropharmacology, Kerman Neuroscience Research Center, Kerman University of Medical Sciences, Kerman, Iran
| | - Golnaz Shafiei
- Department of anatomy, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
- Anatomical Sciences Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Soodeh Rajabi
- Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Jehad Blvd, Ebn Sina Avenue, Kerman, 76198-13159, Iran.
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Rufo-Martín C, Infante-García D, Díaz-Álvarez J, Miguélez H, Youssef G. Printable and Tunable Bioresin with Strategically Decorated Molecular Structures. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2025; 37:e2412338. [PMID: 39648663 DOI: 10.1002/adma.202412338] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Revised: 11/07/2024] [Indexed: 12/10/2024]
Abstract
As personalized medicine rapidly evolves, there is a critical demand for advanced biocompatible materials surpassing current additive manufacturing capabilities. This study presents a novel printable bioresin engineered with tunable mechanical, thermal, and biocompatibility properties through strategic molecular modifications. The study introduces a new bioresin comprising methyl methacrylate (MMA), ethylene glycol dimethacrylate (EGDMA), and a photoinitiator, which is further enhanced by incorporating high molecular weight polymethyl methacrylate (PMMA) to improve biostability and mechanical performance. The integration of printable PMMA presents several synthesis and processing challenges, necessitating substantial modifications to the 3D printing process. Additionally, the bioresin is functionalized with antibacterial silver oxide and bone-growth-promoting hydroxyapatite at various weight ratios to extend its application further. The results demonstrate the agile printability of the novel bioresin and its potential for transformative impact in biomedical applications, offering a versatile material platform for additive manufacturing-enabled personalized medicine. This work highlights the adaptability of the novel printable bioresin for real-life applications and its capacity for multiscale structural tailoring, potentially achieving properties comparable to native tissues and extending beyond conventional additive manufacturing techniques.
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Affiliation(s)
- Celia Rufo-Martín
- Experimental Mechanics Laboratory, Mechanical Engineering Department, San Diego State University, 5500 Campanile Drive, San Diego, CA, 92182, USA
- Advanced Manufacturing Hub, San Diego State University, 5500 Campanile Drive, San Diego, CA, 92182, USA
- Department of Mechanical Engineering, Universidad Carlos III de Madrid, Avda. de la Universidad 30, Leganés, 28911, Madrid, Spain
| | - Diego Infante-García
- Institute of Mechanical and Biomechanical Engineering, I2MB, Department of Mechanical Engineering and Materials, Universitat Politècnica de València, Camino de Vera, Valencia, 46022, Spain
| | - José Díaz-Álvarez
- Department of Mechanical Engineering, Universidad Carlos III de Madrid, Avda. de la Universidad 30, Leganés, 28911, Madrid, Spain
| | - Henar Miguélez
- Department of Mechanical Engineering, Universidad Carlos III de Madrid, Avda. de la Universidad 30, Leganés, 28911, Madrid, Spain
| | - George Youssef
- Experimental Mechanics Laboratory, Mechanical Engineering Department, San Diego State University, 5500 Campanile Drive, San Diego, CA, 92182, USA
- Advanced Manufacturing Hub, San Diego State University, 5500 Campanile Drive, San Diego, CA, 92182, USA
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Ding JY, Meng TT, Du RL, Song XB, Li YX, Gao J, Ji R, He QY. Bibliometrics of trends in global research on the roles of stem cells in myocardial fibrosis therapy. World J Stem Cells 2024; 16:1086-1105. [PMID: 39734477 PMCID: PMC11669986 DOI: 10.4252/wjsc.v16.i12.1086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2024] [Revised: 10/05/2024] [Accepted: 11/11/2024] [Indexed: 12/13/2024] Open
Abstract
BACKGROUND Myocardial fibrosis, a condition linked to several cardiovascular diseases, is associated with a poor prognosis. Stem cell therapy has emerged as a potential treatment option and the application of stem cell therapy has been studied extensively. However, a comprehensive bibliometric analysis of these studies has yet to be conducted. AIM To map thematic trends, analyze research hotspots, and project future directions of stem cell-based myocardial fibrosis therapy. METHODS We conducted a bibliometric and visual analysis of studies in the Web of Science Core Collection using VOSviewer and Microsoft Excel. The dataset included 1510 articles published between 2001 and 2024. Countries, organizations, authors, references, keywords, and co-citation networks were examined to identify evolving research trends. RESULTS Our findings revealed a steady increase in the number of publications, with a projected increase to over 200 publications annually by 2030. Initial research focused on stem cell-based therapy, particularly for myocardial infarction and heart failure. More recently, there has been a shift toward cell-free therapy, involving extracellular vesicles, exosomes, and microRNAs. Key research topics include angiogenesis, inflammation, apoptosis, autophagy, and oxidative stress. CONCLUSION This analysis highlights the evolution of stem cell therapies for myocardial fibrosis, with emerging interest in cell-free approaches. These results are expected to guide future scientific exploration and decision-making.
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Affiliation(s)
- Jing-Yi Ding
- Department of Cardiology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Tian-Tian Meng
- Department of Rehabilitation, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing 100071, China
| | - Ruo-Lin Du
- Department of Emergency Medicine, South Branch of Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Xin-Bin Song
- Department of Intensive Care Unit, Zhumadian Hospital of Traditional Chinese Medicine, Zhumadian 463000, Henan Province, China
| | - Yi-Xiang Li
- Department of Chinese Medicine, The Third People's Hospital of Henan Province, Zhengzhou 450000 Henan Province, China
| | - Jing Gao
- Department of Cardiology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Ran Ji
- Department of Intensive Care Unit, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Qing-Yong He
- Department of Cardiology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China.
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Zhang YX, Zhou Y, Xiong YY, Li YM. Beyond skin deep: Revealing the essence of iPS cell-generated skin organoids in regeneration. Burns 2024; 50:107194. [PMID: 39317530 DOI: 10.1016/j.burns.2024.06.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2023] [Revised: 03/13/2024] [Accepted: 06/23/2024] [Indexed: 09/26/2024]
Abstract
Various methods have been used for in vivo and in vitro skin regeneration, including stem cell therapy, tissue engineering, 3D printing, and platelet-rich plasma (PRP) injection therapy. However, these approaches are rooted in the existing knowledge of skin structures, which overlook the normal physiological processes of skin development and fall short of replicating the skin's regenerative processes outside the body. This comprehensive review primarily focuses on skin organoids derived from human pluripotent stem cells, which have the capacity to regenerate human skin tissue by restoring the embryonic skin structure, thus offering a novel avenue for producing in vitro skin substitutes. Furthermore, they contribute to the repair of damaged skin lesions in patients with systemic sclerosis or severe burns. Particular emphasis will be placed on the origins, generations, and applications of skin organoids, especially in dermatology, and the challenges that must be addressed before clinical implementation.
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Affiliation(s)
- Yu-Xuan Zhang
- Institute of Regenerative Medicine, and Department of Dermatology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, China
| | - Yuan Zhou
- Institute of Regenerative Medicine, and Department of Dermatology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, China
| | - Yu-Yun Xiong
- Institute of Regenerative Medicine, and Department of Dermatology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, China.
| | - Yu-Mei Li
- Institute of Regenerative Medicine, and Department of Dermatology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, China.
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Otani K, Zeniya T, Kawashima H, Moriguchi T, Nakano A, Han C, Murata S, Nishimura K, Koshino K, Yamahara K, Inubushi M, Iida H. Spatial and temporal tracking of multi-layered cells sheet using reporter gene imaging with human sodium iodide symporter: a preclinical study using a rat model of myocardial infarction. Eur J Nucl Med Mol Imaging 2024; 52:74-87. [PMID: 39207487 PMCID: PMC11599416 DOI: 10.1007/s00259-024-06889-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2024] [Accepted: 08/14/2024] [Indexed: 09/04/2024]
Abstract
PURPOSE This study aimed to evaluate a novel technique for cell tracking by visualising the activity of the human sodium/iodide symporter (hNIS) after transplantation of hNIS-expressing multilayered cell sheets in a rat model of chronic myocardial infarction. METHODS Triple-layered cell sheets were generated from mouse embryonic fibroblasts (MEFs) derived from mice overexpressing hNIS (hNIS-Tg). Myocardial infarction was induced by permanent ligation of the left anterior descending coronary artery in F344 athymic rats, and a triple-layered MEFs sheets were transplanted to the infarcted area two weeks after surgery. To validate the temporal tracking and kinetic analysis of the transplanted MEFs sheets, sequential cardiac single-photon emission computed tomography (SPECT) examinations with a 99mTcO4- injection were performed. The cell sheets generated using MEFs of wild-type mice (WT) served as controls. RESULTS A significantly higher amount of 99mTcO4- was taken into the hNIS-Tg MEFs than into WT MEFs (146.1 ± 30.9-fold). The obvious accumulation of 99mTcO4- was observed in agreement with the region where hNIS-Tg MEFs were transplanted, and these radioactivities peaked 40-60 min after 99mTcO4- administration. The volume of distribution of the hNIS-Tg MEF sheets declined gradually after transplantation, implying cellular malfunction and a loss in the number of transplanted cells. CONCLUSION The reporter gene imaging with hNIS enables the serial tracking and quantitative kinetic analysis of cell sheets transplanted to infarcted hearts.
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Affiliation(s)
- Kentaro Otani
- Department of Molecular Pharmacology, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan
| | - Tsutomu Zeniya
- Graduate School of Science and Technology, Hirosaki University, Aomori, Japan
| | - Hidekazu Kawashima
- Radioisotope Research Center, Kyoto Pharmaceutical University, Kyoto, Japan
| | - Tetsuaki Moriguchi
- Tandem Accelerator Complex (UTTAC), University of Tsukuba, Ibaraki, Japan
| | - Atsushi Nakano
- Department of Research Promotion and Management, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan
| | - Chunlei Han
- Turku PET Centre, Turku University Hospital, Turku, Finland
| | - Shunsuke Murata
- Department of Preventive Medicine and Epidemiology, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan
| | - Kunihiro Nishimura
- Department of Preventive Medicine and Epidemiology, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan
| | - Kazuhiro Koshino
- Department of Systems and Informatics, Hokkaido Information University, Hokkaido, Japan
| | - Kenichi Yamahara
- Laboratory of Molecular and Cellular Therapy, Institute for Advanced Medical Sciences, Hyogo Medical University, Hyogo, Japan
| | - Masayuki Inubushi
- Division of Nuclear Medicine, Department of Radiology, Kawasaki Medical School, Okayama, Japan
| | - Hidehiro Iida
- Turku PET Centre, Turku University Hospital, Turku, Finland.
- Turku PET Centre, University of Turku and Turku University Hospital, Building 14, Kiinamyllynkatu 4-8, Turku, 20520, Finland.
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10
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Hashiguchi R, Ichikawa H, Kumeta M, Koyama D. Control of myotube orientation using ultrasonication. Sci Rep 2024; 14:25737. [PMID: 39468262 PMCID: PMC11519932 DOI: 10.1038/s41598-024-77277-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Accepted: 10/21/2024] [Indexed: 10/30/2024] Open
Abstract
This study investigated a technique for controlling the orientation of C2C12-derived myotube cells using ultrasonication for future clinical applications of cultured skeletal muscle tissues. An ultrasonicating cell culture dish, comprising a plastic-bottomed culture dish and a circular glass plate (diameter, 35 mm; thickness, 1.1 mm) attached to an annular piezoelectric ultrasonic transducer (inner diameter, 10 mm; outer diameter, 20 mm; thickness, 1 mm), was constructed. A concentric resonant vibrational mode at 89 kHz was generated on the bottom of the dish, and the orientations of myotube cells were quantitatively evaluated using two-dimensional Fourier transform analysis of phase contrast microscopy images captured over a 14 × 10 mm2 area at the center of the dish. Unsonicated myotube cells grew in random directions, but ultrasonication aligned them circumferentially in the culture dish. The timing of treatment was important, with ultrasonication for 48 h before differentiation having a greater impact on myotube orientation than ultrasonication after differentiation. A larger ultrasonic vibration, with an amplitude of over 20 Vpp, resulted in significantly smaller angles of deviation in the circumferential direction than the control. Ultrasonication enhanced the expression of differentiation-related genes and the formation of aligned myotubes, suggesting that it promotes differentiation of C2C12 cells into myotubes.
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Affiliation(s)
- Ryohei Hashiguchi
- Faculty of Science and Engineering, Doshisha University, 1-3 TataraMiyakodani, Kyotanabe, Kyoto, 610-0321, Japan
| | - Hidetaka Ichikawa
- Faculty of Science and Engineering, Doshisha University, 1-3 TataraMiyakodani, Kyotanabe, Kyoto, 610-0321, Japan
| | - Masahiro Kumeta
- Graduate School of Biostudies, Kyoto University, Yoshida Konoe, Kyoto, 606-8501, Japan
- Center for Living Systems Information Science (CeLiSIS), Kyoto University, Yoshida Konoe, Kyoto, 606-8501, Japan
| | - Daisuke Koyama
- Faculty of Science and Engineering, Doshisha University, 1-3 TataraMiyakodani, Kyotanabe, Kyoto, 610-0321, Japan.
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11
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Liu Z, Zhao X. piRNAs as emerging biomarkers and physiological regulatory molecules in cardiovascular disease. Biochem Biophys Res Commun 2024; 711:149906. [PMID: 38640879 DOI: 10.1016/j.bbrc.2024.149906] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2024] [Revised: 04/01/2024] [Accepted: 04/05/2024] [Indexed: 04/21/2024]
Abstract
Cardiovascular diseases (CVD) represent one of the most considerable global health threats, owing to their high incidence and mortality rates. Despite the ongoing advancements in detection, prevention, treatment, and prognosis of CVD, which have resulted in a decline in both incidence and mortality rates, CVD remains a major public health concern. Therefore, novel diagnostic biomarkers and therapeutic interventions are imperative to minimise the risk of CVD. Non-coding RNAs (ncRNAs) have recently gained increasing attention, with PIWI-interacting RNAs (piRNAs) emerging as a class of small ncRNAs traditionally recognised for their role in silencing transposons within cells. Although the functional roles of PIWI proteins and piRNAs in human cells remain unclear, growing evidence suggests that these molecules are gradually becoming valuable biomarkers for the diagnosis and treatment of CVD. This review provides a comprehensive summary of the latest studies on piRNAs in CVD. This review discusses the roles of piRNAs in various cardiovascular subtypes, including myocardial hypertrophy, heart failure, myocardial infarction, and cardiac regeneration. The perceived insights may contribute novel perspectives for the diagnosis and treatment of CVD.
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Affiliation(s)
- Zhihua Liu
- School of Basic Medical Sciences, Center for Precision Medicine, Kunming YanAn Hospital & Kunming University of Science and Technology, Kunming, China; Department of Biostatistics and Computational Biology, Bayer HealthCare, Harvard University, Boston, MA, USA.
| | - Xi Zhao
- School of Basic Medical Sciences, Center for Precision Medicine, Kunming YanAn Hospital & Kunming University of Science and Technology, Kunming, China
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12
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Nakao M, Nagase K. Harvesting methods of umbilical cord-derived mesenchymal stem cells from culture modulate cell properties and functions. Regen Ther 2024; 26:80-88. [PMID: 38841206 PMCID: PMC11152751 DOI: 10.1016/j.reth.2024.05.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Revised: 04/11/2024] [Accepted: 05/19/2024] [Indexed: 06/07/2024] Open
Abstract
Introduction Human umbilical cord-derived mesenchymal stem cells (UC-MSCs) are promising candidates for stem cell therapy. Various methods such as enzymatic treatment, cell scraping, and temperature reduction using temperature-responsive cell culture dishes have been employed to culture and harvest UC-MSCs. However, the effects of different harvesting methods on cell properties and functions in vitro remain unclear. In this study, we investigated the properties and functions of UC-MSC using various cell-harvesting methods. Methods UC-MSC suspensions were prepared using treatments with various enzymes, cell scraping, and temperature reduction in temperature-responsive cell culture dishes. UC-MSC sheets were prepared in a temperature-responsive cell culture dish. The properties and functions of the UC-MSC suspensions and sheets were assessed according to Annexin V staining, lactate dehydrogenase (LDH) assay, re-adhesion behavior, and cytokine secretion analysis via enzyme-linked immunosorbent assay. Results Annexin V staining revealed that accutase induced elevated UC-MSC apoptosis. Physical scraping using a cell scraper induced a relatively high LDH release due to damaged cell membranes. Dispase exhibited relatively low adhesion from initial incubation until 3 h. UC-MSC sheets exhibited rapid re-adhesion at 15 min and cell migration at 6 h. UC-MSC sheets expressed higher levels of cytokines such as HGF, TGF-β1, IL-10, and IL-6 than did UC-MSCs in suspension. Conclusions The choice of enzyme and physical scraping methods for harvesting UC-MSCs significantly influenced their activity and function. Thus, selecting appropriate cell-harvesting methods is important for successful stem cell therapy.
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Affiliation(s)
- Mitsuyoshi Nakao
- Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo, 105-8512, Japan
| | - Kenichi Nagase
- Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo, 105-8512, Japan
- Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan
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13
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Razavi ZS, Soltani M, Mahmoudvand G, Farokhi S, Karimi-Rouzbahani A, Farasati-Far B, Tahmasebi-Ghorabi S, Pazoki-Toroudi H, Afkhami H. Advancements in tissue engineering for cardiovascular health: a biomedical engineering perspective. Front Bioeng Biotechnol 2024; 12:1385124. [PMID: 38882638 PMCID: PMC11176440 DOI: 10.3389/fbioe.2024.1385124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2024] [Accepted: 05/13/2024] [Indexed: 06/18/2024] Open
Abstract
Myocardial infarction (MI) stands as a prominent contributor to global cardiovascular disease (CVD) mortality rates. Acute MI (AMI) can result in the loss of a large number of cardiomyocytes (CMs), which the adult heart struggles to replenish due to its limited regenerative capacity. Consequently, this deficit in CMs often precipitates severe complications such as heart failure (HF), with whole heart transplantation remaining the sole definitive treatment option, albeit constrained by inherent limitations. In response to these challenges, the integration of bio-functional materials within cardiac tissue engineering has emerged as a groundbreaking approach with significant potential for cardiac tissue replacement. Bioengineering strategies entail fortifying or substituting biological tissues through the orchestrated interplay of cells, engineering methodologies, and innovative materials. Biomaterial scaffolds, crucial in this paradigm, provide the essential microenvironment conducive to the assembly of functional cardiac tissue by encapsulating contracting cells. Indeed, the field of cardiac tissue engineering has witnessed remarkable strides, largely owing to the application of biomaterial scaffolds. However, inherent complexities persist, necessitating further exploration and innovation. This review delves into the pivotal role of biomaterial scaffolds in cardiac tissue engineering, shedding light on their utilization, challenges encountered, and promising avenues for future advancement. By critically examining the current landscape, we aim to catalyze progress toward more effective solutions for cardiac tissue regeneration and ultimately, improved outcomes for patients grappling with cardiovascular ailments.
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Affiliation(s)
- Zahra-Sadat Razavi
- Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Madjid Soltani
- Department of Mechanical Engineering, K. N. Toosi University of Technology, Tehran, Iran
- Department of Electrical and Computer Engineering, University of Waterloo, Waterloo, ON, Canada
- Centre for Sustainable Business, International Business University, Toronto, ON, Canada
| | - Golnaz Mahmoudvand
- Student Research Committee, USERN Office, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Simin Farokhi
- Student Research Committee, USERN Office, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Arian Karimi-Rouzbahani
- Student Research Committee, USERN Office, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Bahareh Farasati-Far
- Department of Chemistry, Iran University of Science and Technology, Tehran, Iran
| | - Samaneh Tahmasebi-Ghorabi
- Master of Health Education, Research Expert, Clinical Research Development Unit, Emam Khomeini Hospital, Ilam University of Medical Sciences, Ilam, Iran
| | | | - Hamed Afkhami
- Nervous System Stem Cells Research Center, Semnan University of Medical Sciences, Semnan, Iran
- Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran
- Department of Medical Microbiology, Faculty of Medicine, Shahed University, Tehran, Iran
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14
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Guan H, Chen Y, Liu X, Huang L. Research and application of hydrogel-encapsulated mesenchymal stem cells in the treatment of myocardial infarction. Colloids Surf B Biointerfaces 2024; 239:113942. [PMID: 38729022 DOI: 10.1016/j.colsurfb.2024.113942] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Revised: 04/19/2024] [Accepted: 05/02/2024] [Indexed: 05/12/2024]
Abstract
Myocardial infarction (MI) stands out as a highly lethal disease that poses a significant threat to global health. Worldwide, heart failure resulting from MI remains a leading cause of human mortality. Mesenchymal stem cell (MSC) therapy has emerged as a promising therapeutic approach, leveraging its intrinsic healing properties. Nevertheless, pervasive issues, including a low cell retention rate, suboptimal survival rate, and incomplete differentiation of MSCs, present formidable challenges for further research. The introduction and advancement of biomaterials have offered a novel avenue for the exploration of MSC therapy in MI, marking considerable progress thus far. Notably, hydrogels, among the representative biomaterials, have garnered extensive attention within the biomedical field. This review delves into recent advancements, specifically focusing on the application of hydrogels to augment MSC therapy for cardiac tissue regeneration in MI.
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Affiliation(s)
- Haien Guan
- Center of Stem Cell and Regenerative Medicine, Gaozhou People's Hospital, Gaozhou 525200, China
| | - Yuehua Chen
- Center of Stem Cell and Regenerative Medicine, Gaozhou People's Hospital, Gaozhou 525200, China
| | - Xuanyu Liu
- Center of Stem Cell and Regenerative Medicine, Gaozhou People's Hospital, Gaozhou 525200, China
| | - Li Huang
- Center of Stem Cell and Regenerative Medicine, Gaozhou People's Hospital, Gaozhou 525200, China.
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15
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Olatunji G, Kokori E, Yusuf I, Ayanleke E, Damilare O, Afolabi S, Adetunji B, Mohammed S, Akinmoju O, Aboderin G, Aderinto N. Stem cell-based therapies for heart failure management: a narrative review of current evidence and future perspectives. Heart Fail Rev 2024; 29:573-598. [PMID: 37733137 DOI: 10.1007/s10741-023-10351-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/13/2023] [Indexed: 09/22/2023]
Abstract
Heart failure (HF) is a prevalent and debilitating global cardiovascular condition affecting around 64 million individuals, placing significant strain on healthcare systems and diminishing patients' quality of life. The escalating prevalence of HF underscores the urgent need for innovative therapeutic approaches that target the root causes and aim to restore normal cardiac function. Stem cell-based therapies have emerged as promising candidates, representing a fundamental departure from conventional treatments focused primarily on symptom management. This review explores the evolving landscape of stem cell-based therapies for HF management. It delves into the mechanisms of action, clinical evidence from both positive and negative outcomes, ethical considerations, and regulatory challenges. Key findings include the potential for improved cardiac function, enhanced quality of life, and long-term benefits associated with stem cell therapies. However, adverse events and patient vulnerabilities necessitate stringent safety assessments. Future directions in stem cell-based HF therapies include enhancing efficacy and safety through optimized stem cell types, delivery techniques, dosing strategies, and long-term safety assessments. Personalized medicine, combining therapies, addressing ethical and regulatory challenges, and expanding access while reducing costs are crucial aspects of the evolving landscape.
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Affiliation(s)
- Gbolahan Olatunji
- Department of Medicine and Surgery, University of Ilorin, Ilorin, Nigeria
| | - Emmanuel Kokori
- Department of Medicine and Surgery, University of Ilorin, Ilorin, Nigeria
| | - Ismaila Yusuf
- Department of Medicine and Surgery, Obafemi Awolowo University, Osun, Nigeria
| | - Emmanuel Ayanleke
- Department of Medicine and Surgery, University of Ilorin, Ilorin, Nigeria
| | - Olakanmi Damilare
- Department of Medicine and Surgery, Ladoke Akintola University Teaching Hospital, Ogbomoso, Nigeria
| | - Samson Afolabi
- Department of Medicine and Surgery, Ladoke Akintola University Teaching Hospital, Ogbomoso, Nigeria
| | - Busayo Adetunji
- Department of Medicine and Surgery, Ladoke Akintola University Teaching Hospital, Ogbomoso, Nigeria
| | - Saad Mohammed
- Al-Kindy College of Medicine, University of Baghdad, Baghdad, Iraq
| | | | - Gbolahan Aboderin
- Department of Medicine and Surgery, Ladoke Akintola University Teaching Hospital, Ogbomoso, Nigeria
| | - Nicholas Aderinto
- Department of Medicine and Surgery, Ladoke Akintola University Teaching Hospital, Ogbomoso, Nigeria.
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16
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Li M, Yang T, Zhao J, Ma X, Cao Y, Hu X, Zhao S, Zhou L. Cell sheet formation enhances the therapeutic effects of adipose-derived stromal vascular fraction on urethral stricture. Mater Today Bio 2024; 25:101012. [PMID: 38464495 PMCID: PMC10924207 DOI: 10.1016/j.mtbio.2024.101012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2023] [Revised: 02/15/2024] [Accepted: 02/26/2024] [Indexed: 03/12/2024] Open
Abstract
Urethral stricture (US) is a common disease in urology, lacking effective treatment options. Although injecting a stem cells suspension into the affected area has shown therapeutic benefits, challenges such as low retention rate and limited efficacy hinder the clinical application of stem cells. This study evaluates the therapeutic impact and the mechanism of adipose-derived vascular fraction (SVF) combined with cell sheet engineering technique on urethral fibrosis in a rat model of US. The results showed that SVF-cell sheets exhibit positive expression of α-SMA, CD31, CD34, Stro-1, and eNOS. In vivo study showed less collagen deposition, low urethral fibrosis, and minimal tissue alteration in the group receiving cell sheet transplantation. Furthermore, the formation of a three-dimensional (3D) tissue-like structure by the cell sheets enhances the paracrine effect of SVF, facilitates the infiltration of M2 macrophages, and suppresses the TGF-β/Smad2 pathway through HGF secretion, thereby exerting antifibrotic effects. Small animal in vivo imaging demonstrates improved retention of SVF cells at the damaged urethra site with cell sheet application. Our results suggest that SVF combined with cell sheet technology more efficiently inhibits the early stages of urethral fibrosis.
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Affiliation(s)
- Muxin Li
- General Clinical Research Center, Nanjing First Hospital, China Pharmaceutical University, Nanjing, Jiangsu, China
| | - Tianli Yang
- Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Jun Zhao
- Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Xinghua Ma
- General Clinical Research Center, Nanjing First Hospital, China Pharmaceutical University, Nanjing, Jiangsu, China
| | - Yuanyuan Cao
- General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Xiaojie Hu
- General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Shuli Zhao
- General Clinical Research Center, Nanjing First Hospital, China Pharmaceutical University, Nanjing, Jiangsu, China
- General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Liuhua Zhou
- Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
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17
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Kavand A, Noverraz F, Gerber-Lemaire S. Recent Advances in Alginate-Based Hydrogels for Cell Transplantation Applications. Pharmaceutics 2024; 16:469. [PMID: 38675129 PMCID: PMC11053880 DOI: 10.3390/pharmaceutics16040469] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Revised: 03/19/2024] [Accepted: 03/20/2024] [Indexed: 04/28/2024] Open
Abstract
With its exceptional biocompatibility, alginate emerged as a highly promising biomaterial for a large range of applications in regenerative medicine. Whether in the form of microparticles, injectable hydrogels, rigid scaffolds, or bioinks, alginate provides a versatile platform for encapsulating cells and fostering an optimal environment to enhance cell viability. This review aims to highlight recent studies utilizing alginate in diverse formulations for cell transplantation, offering insights into its efficacy in treating various diseases and injuries within the field of regenerative medicine.
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Affiliation(s)
| | | | - Sandrine Gerber-Lemaire
- Group for Functionalized Biomaterials, Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland; (A.K.); (F.N.)
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18
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Manskikh VN. Organ Frame Elements or Free Intercellular Gel-Like Matrix as Necessary Conditions for Building Organ Structures during Regeneration. BIOCHEMISTRY. BIOKHIMIIA 2024; 89:269-278. [PMID: 38622095 DOI: 10.1134/s000629792402007x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Revised: 11/02/2023] [Accepted: 11/15/2023] [Indexed: 04/17/2024]
Abstract
Over the past decades, an unimaginably large number of attempts have been made to restore the structure of mammalian organs after injury by introducing stem cells into them. However, this procedure does not lead to full recovery. At the same time, it is known that complete regeneration (restitution without fibrosis) is possible in organs with proliferating parenchymal cells. An analysis of such models allows to conclude that the most important condition for the repair of histological structures of an organ (in the presence of stem cells) is preservation of the collagen frame structures in it, which serve as "guide rails" for proliferating and differentiating cells. An alternative condition for complete reconstruction of organ structures is the presence of a free "morphogenetic space" containing a gel-like matrix of the embryonic-type connective tissue, which exists during embryonal development of organs in mammals or during complete regeneration in amphibians. Approaches aimed at preserving frame structures or creating a "morphogenetic space" could radically improve the results of organ regeneration using both local and exogenous stem cells.
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Affiliation(s)
- Vasily N Manskikh
- Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119991, Russia.
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19
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Netsrithong R, Garcia-Perez L, Themeli M. Engineered T cells from induced pluripotent stem cells: from research towards clinical implementation. Front Immunol 2024; 14:1325209. [PMID: 38283344 PMCID: PMC10811463 DOI: 10.3389/fimmu.2023.1325209] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Accepted: 12/15/2023] [Indexed: 01/30/2024] Open
Abstract
Induced pluripotent stem cell (iPSC)-derived T (iT) cells represent a groundbreaking frontier in adoptive cell therapies with engineered T cells, poised to overcome pivotal limitations associated with conventional manufacturing methods. iPSCs offer an off-the-shelf source of therapeutic T cells with the potential for infinite expansion and straightforward genetic manipulation to ensure hypo-immunogenicity and introduce specific therapeutic functions, such as antigen specificity through a chimeric antigen receptor (CAR). Importantly, genetic engineering of iPSC offers the benefit of generating fully modified clonal lines that are amenable to rigorous safety assessments. Critical to harnessing the potential of iT cells is the development of a robust and clinically compatible production process. Current protocols for genetic engineering as well as differentiation protocols designed to mirror human hematopoiesis and T cell development, vary in efficiency and often contain non-compliant components, thereby rendering them unsuitable for clinical implementation. This comprehensive review centers on the remarkable progress made over the last decade in generating functional engineered T cells from iPSCs. Emphasis is placed on alignment with good manufacturing practice (GMP) standards, scalability, safety measures and quality controls, which constitute the fundamental prerequisites for clinical application. In conclusion, the focus on iPSC as a source promises standardized, scalable, clinically relevant, and potentially safer production of engineered T cells. This groundbreaking approach holds the potential to extend hope to a broader spectrum of patients and diseases, leading in a new era in adoptive T cell therapy.
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Affiliation(s)
- Ratchapong Netsrithong
- Department of Hematology, Amsterdam University Medical Center (UMC), Vrije Universiteit Amsterdam, Amsterdam, Netherlands
- Cancer Biology and Immunology, Cancer Center Amsterdam, Amsterdam, Netherlands
| | - Laura Garcia-Perez
- Department of Hematology, Amsterdam University Medical Center (UMC), Vrije Universiteit Amsterdam, Amsterdam, Netherlands
- Cancer Biology and Immunology, Cancer Center Amsterdam, Amsterdam, Netherlands
| | - Maria Themeli
- Department of Hematology, Amsterdam University Medical Center (UMC), Vrije Universiteit Amsterdam, Amsterdam, Netherlands
- Cancer Biology and Immunology, Cancer Center Amsterdam, Amsterdam, Netherlands
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20
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Deng B, Deng W, Zheng H, Wei Y, Zhang J, Zeng N, He Y, Guo R. Non-adherent culture method affects the proliferation and apoptosis of mesenchymal stem cells through inhibiting LINC00707 to promote RNF6-mediated QKI ubiquitination. Exp Cell Res 2024; 434:113877. [PMID: 38072302 DOI: 10.1016/j.yexcr.2023.113877] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Revised: 11/15/2023] [Accepted: 12/03/2023] [Indexed: 12/17/2023]
Abstract
Exploration of the molecular mechanisms of mesenchymal stem cell (MSC) growth has significant clinical benefits. Long non-coding RNAs (lncRNAs) have been reported to play vital roles in the regulation of the osteogenic differentiation of MSCs. However, the mechanism by which lncRNA affects the proliferation and apoptosis of MSCs is unclear. In this study, sequencing analysis revealed that LINC00707 was significantly decreased in non-adherent human MSCs (non-AC-hMSCs) compared to adherent human MSCs. Moreover, LINC00707 overexpression promoted non-AChMSC proliferation, cell cycle progression from the G0/G1 phase to the S phase and inhibited apoptosis, whereas LINC00707 silencing had the opposite effect. Furthermore, LINC00707 interacted directly with the quaking (QKI) protein and enhanced the E3 ubiquitin-protein ligase ring finger protein 6 (RNF6)-mediated ubiquitination of the QKI protein. Additionally, the overexpression of QKI rescued the promotive effects on proliferation and inhibitory effects on apoptosis in non-AC-hMSCs induced by the ectopic expression of LINC00707. Thus, LINC00707 contributes to the proliferation and apoptosis in non-AChMSCs by regulating the ubiquitination and degradation of the QKI protein.
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Affiliation(s)
- Baoping Deng
- Department of Interventional Vascular Surgery, The Fifth Affiliated Hospital, Southern Medical University, 566# Congcheng Road, Conghua District, Guangzhou, Guangdong Province, PR China; Department of Vascular Surgery, Affiliated Hospital of Guilin Medical University, Guilin, 541001, PR China
| | - Weiping Deng
- Department of Gastroenterology, Shenzhen Longhua District Central Hospital, 187# Guan Lan Road, Longhua District, Shenzhen, 518110, Guangdong, PR China
| | - Hongmei Zheng
- Department of Gastroenterology, Shenzhen Longhua District Central Hospital, 187# Guan Lan Road, Longhua District, Shenzhen, 518110, Guangdong, PR China
| | - Yue Wei
- Maternal and Child Research Institute, Shunde Women and Children's Hospital of Guangdong Medical University, No. 3 Baojian Road, Shunde district, Foshan 528300, PR China
| | - Jinfeng Zhang
- Maternal and Child Research Institute, Shunde Women and Children's Hospital of Guangdong Medical University, No. 3 Baojian Road, Shunde district, Foshan 528300, PR China
| | - Na Zeng
- Maternal and Child Research Institute, Shunde Women and Children's Hospital of Guangdong Medical University, No. 3 Baojian Road, Shunde district, Foshan 528300, PR China
| | - Yulan He
- Maternal and Child Research Institute, Shunde Women and Children's Hospital of Guangdong Medical University, No. 3 Baojian Road, Shunde district, Foshan 528300, PR China
| | - Runmin Guo
- Maternal and Child Research Institute, Shunde Women and Children's Hospital of Guangdong Medical University, No. 3 Baojian Road, Shunde district, Foshan 528300, PR China.
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21
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Nakao M, Matsui M, Kim K, Nishiyama N, Grainger DW, Okano T, Kanazawa H, Nagase K. Umbilical cord-derived mesenchymal stem cell sheets transplanted subcutaneously enhance cell retention and survival more than dissociated stem cell injections. Stem Cell Res Ther 2023; 14:352. [PMID: 38072920 PMCID: PMC10712142 DOI: 10.1186/s13287-023-03593-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Accepted: 11/29/2023] [Indexed: 12/18/2023] Open
Abstract
BACKGROUND Human umbilical cord-derived mesenchymal stem cell (hUC-MSC) sheets have recently attracted attention as an alternative approach to injected cell suspensions for stem cell therapy. However, cell engraftment and cytokine expression levels between hUC-MSC sheets and their cell suspensions in vivo have not yet been compared. This study compares hUC-MSC in vivo engraftment efficacy and cytokine expression for both hUC-MSC sheets and cell suspensions. METHODS hUC-MSC sheets were prepared using temperature-responsive cell culture; two types of hUC-MSC suspensions were prepared, either by enzymatic treatment (trypsin) or by enzyme-free temperature reduction using temperature-responsive cell cultureware. hUC-MSC sheets and suspensions were transplanted subcutaneously into ICR mice through subcutaneous surgical placement and intravenous injection, respectively. hUC-MSC sheet engraftment after subcutaneous surgical transplantation was investigated by in vivo imaging while intravenously injected cell suspensions were analyzing using in vitro organ imaging. Cytokine levels in both transplant site tissues and blood were quantified by enzyme-linked immunosorbent assay. RESULTS After subcutaneous transplant, hUC-MSC sheets exhibited longer engraftment duration than hUC-MSC suspensions. This was attributed to extracellular matrix (ECM) and cell-cell junctions retained in sheets but enzymatically altered in suspensions. hUC-MSC suspensions harvested using enzyme-free temperature reduction exhibited relatively long engraftment duration after intravenous injection compared to suspensions prepared using trypsin, as enzyme-free harvest preserved cellular ECM. High HGF and TGF-β1 levels were observed in sheet-transplanted sites compared to hUC-MSC suspension sites. However, no differences in human cytokine levels in murine blood were detected, indicating that hUC-MSC sheets might exert local paracrine rather than endocrine effects. CONCLUSIONS hUC-MSC sheet transplantation could be a more effective cell therapeutic approach due to enhanced engraftment and secretion of therapeutic cytokines over injected hUC-MSC suspensions.
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Affiliation(s)
- Mitsuyoshi Nakao
- Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo, 105-8512, Japan
| | - Makoto Matsui
- Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa, 226-8503, Japan
| | - Kyungsook Kim
- Cell Sheet Tissue Engineering Center (CSTEC), Department of Molecular Pharmaceutics, University of Utah, Health Sciences, Salt Lake City, UT, 84112, USA
| | - Nobuhiro Nishiyama
- Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa, 226-8503, Japan
| | - David W Grainger
- Cell Sheet Tissue Engineering Center (CSTEC), Department of Molecular Pharmaceutics, University of Utah, Health Sciences, Salt Lake City, UT, 84112, USA
- Department of Biomedical Engineering, University of Utah, Salt Lake City, UT, 84112, USA
| | - Teruo Okano
- Cell Sheet Tissue Engineering Center (CSTEC), Department of Molecular Pharmaceutics, University of Utah, Health Sciences, Salt Lake City, UT, 84112, USA
| | - Hideko Kanazawa
- Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo, 105-8512, Japan
| | - Kenichi Nagase
- Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo, 105-8512, Japan.
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22
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Qian B, Shen A, Huang S, Shi H, Long Q, Zhong Y, Qi Z, He X, Zhang Y, Hai W, Wang X, Cui Y, Chen Z, Xuan H, Zhao Q, You Z, Ye X. An Intrinsically Magnetic Epicardial Patch for Rapid Vascular Reconstruction and Drug Delivery. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2023; 10:e2303033. [PMID: 37964406 PMCID: PMC10754083 DOI: 10.1002/advs.202303033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Revised: 08/30/2023] [Indexed: 11/16/2023]
Abstract
Myocardial infarction (MI) is a major cause of mortality worldwide. The major limitation of regenerative therapy for MI is poor cardiac retention of therapeutics, which results from an inefficient vascular network and poor targeting ability. In this study, a two-layer intrinsically magnetic epicardial patch (MagPatch) prepared by 3D printing with biocompatible materials like poly (glycerol sebacate) (PGS) is designed, poly (ε-caprolactone) (PCL), and NdFeB. The two-layer structure ensured that the MagPatch multifariously utilized the magnetic force for rapid vascular reconstruction and targeted drug delivery. MagPatch accumulates superparamagnetic iron oxide (SPION)-labelled endothelial cells, instantly forming a ready-implanted organization, and rapidly reconstructs a vascular network anastomosed with the host. In addition, the prefabricated vascular network within the MagPatch allowed for the efficient accumulation of SPION-labelled therapeutics, amplifying the therapeutic effects of cardiac repair. This study defined an extendable therapeutic platform for vascularization-based targeted drug delivery that is expected to assist in the progress of regenerative therapies in clinical applications.
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Affiliation(s)
- Bei Qian
- Department of Cardiovascular Surgery, Ruijin HospitalShanghai Jiaotong University School of MedicineShanghai200025China
| | - Ao Shen
- State Key Laboratory for Modification of Chemical Fibers and Polymer MaterialsCollege of Materials Science and EngineeringInstitute of Functional MaterialsResearch Base of Textile Materials for Flexible Electronics and Biomedical Applications (China Textile Engineering Society)Shanghai Engineering Research Center of Nano‐Biomaterials and Regenerative MedicineDonghua UniversityShanghai201620China
| | - Shixing Huang
- Department of Cardiovascular Surgery, Ruijin HospitalShanghai Jiaotong University School of MedicineShanghai200025China
| | - Hongpeng Shi
- Department of Cardiovascular Surgery, Ruijin HospitalShanghai Jiaotong University School of MedicineShanghai200025China
| | - Qiang Long
- Department of Cardiovascular Surgery, Ruijin HospitalShanghai Jiaotong University School of MedicineShanghai200025China
| | - Yiming Zhong
- Department of Cardiovascular Surgery, Ruijin HospitalShanghai Jiaotong University School of MedicineShanghai200025China
| | - Zhaoxi Qi
- Department of Cardiovascular Surgery, Ruijin HospitalShanghai Jiaotong University School of MedicineShanghai200025China
| | - Xiaojun He
- Department of Cardiovascular Surgery, Ruijin HospitalShanghai Jiaotong University School of MedicineShanghai200025China
| | - Yecen Zhang
- Department of Cardiovascular Surgery, Ruijin HospitalShanghai Jiaotong University School of MedicineShanghai200025China
| | - Wangxi Hai
- Department of Nuclear Medicine, Ruijin HospitalShanghai Jiaotong University School of MedicineShanghai200025China
| | - Xinming Wang
- Department of Cardiovascular Surgery, Ruijin HospitalShanghai Jiaotong University School of MedicineShanghai200025China
| | - Yanna Cui
- Department of Pharmacology and Chemical BiologyShanghai Jiaotong University School of MedicineShanghai200000China
| | - Ziheng Chen
- School of Mechatronics Engineering and AutomationShanghai UniversityShanghai200000China
| | - Huixia Xuan
- State Key Laboratory for Modification of Chemical Fibers and Polymer MaterialsCollege of Materials Science and EngineeringInstitute of Functional MaterialsResearch Base of Textile Materials for Flexible Electronics and Biomedical Applications (China Textile Engineering Society)Shanghai Engineering Research Center of Nano‐Biomaterials and Regenerative MedicineDonghua UniversityShanghai201620China
| | - Qiang Zhao
- Department of Cardiovascular Surgery, Ruijin HospitalShanghai Jiaotong University School of MedicineShanghai200025China
| | - Zhengwei You
- State Key Laboratory for Modification of Chemical Fibers and Polymer MaterialsCollege of Materials Science and EngineeringInstitute of Functional MaterialsResearch Base of Textile Materials for Flexible Electronics and Biomedical Applications (China Textile Engineering Society)Shanghai Engineering Research Center of Nano‐Biomaterials and Regenerative MedicineDonghua UniversityShanghai201620China
| | - Xiaofeng Ye
- Department of Cardiovascular Surgery, Ruijin HospitalShanghai Jiaotong University School of MedicineShanghai200025China
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23
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Thamrin AMH, Soetisna TW, Ramadhani ANE, Hendarto H. Cell sheet transplantation for ischemic heart disease: a systematic review. Indian J Thorac Cardiovasc Surg 2023; 39:577-587. [PMID: 37885940 PMCID: PMC10597942 DOI: 10.1007/s12055-023-01554-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Revised: 05/30/2023] [Accepted: 06/01/2023] [Indexed: 10/28/2023] Open
Abstract
OBJECTIVE Cell sheet transplantation is emerging as an appealing alternative for ischemic heart disease patients as it potentially can increase stem cell viability and retention. But the outcomes and safety of this treatment are still limited in literature and the result varies widely. We conduct a systematic review to look at the efficacy and safety of this promising transplantation method. METHODS A systematic review was performed according to PRISMA guidelines. A comprehensive literature search was undertaken using the PubMed, Scopus, and Embase databases. Articles were thoroughly evaluated and analyzed. RESULTS Seven publications about cell sheet transplantation for ischemic heart disease patients were included. The primary outcomes measured were left ventricular ejection fraction (LVEF) and New York Heart Association (NYHA) class. Safety measurement was depicted by cardiac-related readmission and deaths. The follow-up time ranged from 3 to 36 months for clinical outcomes and 8.5 years for safety outcomes. Cell sheet transplantation showed improvement in LVEF and NYHA class in most studies. Cardiac-related readmission and adverse events of cell sheet transplantation range from 0 to 30.4%, all were nonfatal as no cardiac-related death was reported. Patient preoperative status seems can affect the patient's response to cell sheet therapy. CONCLUSION Cell sheet transplantation can safely improve LVEF and NYHA class in ischemic heart disease patients, even in very low ejection fraction patients with unsuccessful standard therapy before. Further studies with better patient inclusion, larger population, and long-term follow-up required to confirm these results.
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Affiliation(s)
- Ahmad Muslim Hidayat Thamrin
- Adult Cardiac Surgery Division, Department of Thoracic and Cardiovascular Surgery, Harapan Kita National Cardiovascular Center Hospital, S. Parman Street Cavling 87, Jakarta, Indonesia
- Faculty of Medicine Syarif Hidayatullah State Islamic University – Haji Hospital, Jakarta, Indonesia
| | - Tri Wisesa Soetisna
- Adult Cardiac Surgery Division, Department of Thoracic and Cardiovascular Surgery, Harapan Kita National Cardiovascular Center Hospital, S. Parman Street Cavling 87, Jakarta, Indonesia
- Department of Thoracic and Cardiovascular Surgery, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia
| | - Andi Nurul Erisya Ramadhani
- Adult Cardiac Surgery Division, Department of Thoracic and Cardiovascular Surgery, Harapan Kita National Cardiovascular Center Hospital, S. Parman Street Cavling 87, Jakarta, Indonesia
| | - Hari Hendarto
- Faculty of Medicine Syarif Hidayatullah State Islamic University – Haji Hospital, Jakarta, Indonesia
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24
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Bernava G, Iop L. Advances in the design, generation, and application of tissue-engineered myocardial equivalents. Front Bioeng Biotechnol 2023; 11:1247572. [PMID: 37811368 PMCID: PMC10559975 DOI: 10.3389/fbioe.2023.1247572] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2023] [Accepted: 08/29/2023] [Indexed: 10/10/2023] Open
Abstract
Due to the limited regenerative ability of cardiomyocytes, the disabling irreversible condition of myocardial failure can only be treated with conservative and temporary therapeutic approaches, not able to repair the damage directly, or with organ transplantation. Among the regenerative strategies, intramyocardial cell injection or intravascular cell infusion should attenuate damage to the myocardium and reduce the risk of heart failure. However, these cell delivery-based therapies suffer from significant drawbacks and have a low success rate. Indeed, cardiac tissue engineering efforts are directed to repair, replace, and regenerate native myocardial tissue function. In a regenerative strategy, biomaterials and biomimetic stimuli play a key role in promoting cell adhesion, proliferation, differentiation, and neo-tissue formation. Thus, appropriate biochemical and biophysical cues should be combined with scaffolds emulating extracellular matrix in order to support cell growth and prompt favorable cardiac microenvironment and tissue regeneration. In this review, we provide an overview of recent developments that occurred in the biomimetic design and fabrication of cardiac scaffolds and patches. Furthermore, we sift in vitro and in situ strategies in several preclinical and clinical applications. Finally, we evaluate the possible use of bioengineered cardiac tissue equivalents as in vitro models for disease studies and drug tests.
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Affiliation(s)
| | - Laura Iop
- Department of Cardiac Thoracic Vascular Sciences and Public Health, Padua Medical School, University of Padua, Padua, Italy
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25
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Wei X, Wang L, Duan C, Chen K, Li X, Guo X, Chen P, Liu H, Fan Y. Cardiac patches made of brown adipose-derived stem cell sheets and conductive electrospun nanofibers restore infarcted heart for ischemic myocardial infarction. Bioact Mater 2023; 27:271-287. [PMID: 37122901 PMCID: PMC10130885 DOI: 10.1016/j.bioactmat.2023.03.023] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Revised: 03/26/2023] [Accepted: 03/30/2023] [Indexed: 05/02/2023] Open
Abstract
Cell sheet engineering has been proven to be a promising strategy for cardiac remodeling post-myocardial infarction. However, insufficient mechanical strength and low cell retention lead to limited therapeutic efficiency. The thickness and area of artificial cardiac patches also affect their therapeutic efficiency. Cardiac patches prepared by combining cell sheets with electrospun nanofibers, which can be transplanted and sutured to the surface of the infarcted heart, promise to solve this problem. Here, we fabricated a novel cardiac patch by stacking brown adipose-derived stem cells (BADSCs) sheet layer by layer, and then they were combined with multi-walled carbon nanotubes (CNTs)-containing electrospun polycaprolactone/silk fibroin nanofibers (CPSN). The results demonstrated that BADSCs tended to generate myocardium-like structures seeded on CPSN. Compared with BADSCs suspension-containing electrospun nanofibers, the transplantation of the CPSN-BADSCs sheets (CNBS) cardiac patches exhibited accelerated angiogenesis and decreased inflammation in a rat myocardial infarction model. In addition, the CNBS cardiac patches could regulate macrophage polarization and promote gap junction remodeling, thus restoring cardiac functions. Overall, the hybrid cardiac patches made of electrospun nanofibers and cell sheets provide a novel solution to cardiac remodeling after ischemic myocardial infarction.
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Affiliation(s)
- Xinbo Wei
- Key Laboratory for Biomechanics and Mechanobiology (Beihang University) of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, 100083, PR China
| | - Li Wang
- Key Laboratory for Biomechanics and Mechanobiology (Beihang University) of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, 100083, PR China
| | - Cuimi Duan
- Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences, Beijing, 100850, PR China
| | - Kai Chen
- Key Laboratory for Biomechanics and Mechanobiology (Beihang University) of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, 100083, PR China
| | - Xia Li
- Beijing Citident Stomatology Hospital, Beijing, 100032, PR China
| | - Ximin Guo
- Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences, Beijing, 100850, PR China
| | - Peng Chen
- Department of Ultrasound, The Third Medical Center, Chinese PLA General Hospital, Beijing, PR China
| | - Haifeng Liu
- Key Laboratory for Biomechanics and Mechanobiology (Beihang University) of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, 100083, PR China
| | - Yubo Fan
- Key Laboratory for Biomechanics and Mechanobiology (Beihang University) of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, 100083, PR China
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26
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Bui TQ, Binh NT, Pham TLB, Le Van T, Truong NH, Nguyen DPH, Luu TTT, Nguyen-Xuan Pham T, Cam Tran T, Nguyen HTT, Thuy-Trinh N, Tran PA. The Efficacy of Transplanting Human Umbilical Cord Mesenchymal Stem Cell Sheets in the Treatment of Myocardial Infarction in Mice. Biomedicines 2023; 11:2187. [PMID: 37626684 PMCID: PMC10452263 DOI: 10.3390/biomedicines11082187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Revised: 07/17/2023] [Accepted: 07/21/2023] [Indexed: 08/27/2023] Open
Abstract
The transplantation of mesenchymal stem cell (MSC) sheets derived from human umbilical cords (hUCs) was investigated in this study as a potential application in treating myocardial infarction (MI). Two groups of hUC-MSC sheets were formed by populating LunaGelTM, which are 3D scaffolds of photo-crosslinkable gelatin-based hydrogel with two different cell densities. An MI model was created by ligating the left anterior descending coronary artery of healthy BALB/c mice. After two weeks, the cell sheets were applied directly to the MI area and the efficacy of the treatment was evaluated over the next two weeks by monitoring the mice's weight, evaluating the left ventricle ejection fraction, and assessing the histology of the heart tissue at the end of the experiment. Higher cell density showed significantly greater efficiency in MI mice treatment in terms of weight gain and the recovery of ejection fraction. The heart tissue of the groups receiving cell sheets showed human-CD44-positive staining and reduced fibrosis and apoptosis. In conclusion, the hUC-MSC sheets ameliorated heart MI injury in mice and the efficacy of the cell sheets improved as the number of cells increased.
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Affiliation(s)
| | - Nguyen Trong Binh
- Biotechnology Center of Ho Chi Minh City, Ho Chi Minh City 700000, Vietnam; (T.L.-B.P.); (D.P.-H.N.); (T.N.-X.P.)
| | - Truc Le-Buu Pham
- Biotechnology Center of Ho Chi Minh City, Ho Chi Minh City 700000, Vietnam; (T.L.-B.P.); (D.P.-H.N.); (T.N.-X.P.)
- Faculty of Biotechnology, Ho Chi Minh City Open University, Ho Chi Minh City 700000, Vietnam
| | - Trinh Le Van
- Laboratory of Stem Cell Research and Application, University of Science, Ho Chi Minh City 700000, Vietnam; (T.L.V.); (N.H.T.)
- Vietnam National University, Ho Chi Minh City 700000, Vietnam;
| | - Nhung Hai Truong
- Laboratory of Stem Cell Research and Application, University of Science, Ho Chi Minh City 700000, Vietnam; (T.L.V.); (N.H.T.)
- Vietnam National University, Ho Chi Minh City 700000, Vietnam;
| | - Dang Phu-Hai Nguyen
- Biotechnology Center of Ho Chi Minh City, Ho Chi Minh City 700000, Vietnam; (T.L.-B.P.); (D.P.-H.N.); (T.N.-X.P.)
| | - Thao Thi-Thu Luu
- Histology-Embryology-Pathology Department, Faculty of Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City 700000, Vietnam;
| | - Trang Nguyen-Xuan Pham
- Biotechnology Center of Ho Chi Minh City, Ho Chi Minh City 700000, Vietnam; (T.L.-B.P.); (D.P.-H.N.); (T.N.-X.P.)
| | - Tu Cam Tran
- Institute of Tropical Biology, Ho Chi Minh City 700000, Vietnam;
| | - Huyen Thuong-Thi Nguyen
- Divison of Human and Animal Physiology, HCMC University of Education, Ho Chi Minh City 700000, Vietnam;
| | - Nhu Thuy-Trinh
- Vietnam National University, Ho Chi Minh City 700000, Vietnam;
- School of Biomedical Engineering, International University, Ho Chi Minh City 700000, Vietnam
| | - Phong Anh Tran
- Interface Science and Materials Engineering Group, School of Mechanical, Medical and Process Engineering, Faculty of Engineering, Queensland University of Technology, Brisbane City, QLD 4000, Australia;
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27
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Lai P, Sheng M, Ye JH, Tang ZX, Hu S, Wang B, Yuan JL, Yang YH, Zhong YM, Liao YL. Research trends in cardiovascular tissue engineering from 1992 to 2022: a bibliometric analysis. Front Cardiovasc Med 2023; 10:1208227. [PMID: 37593146 PMCID: PMC10427867 DOI: 10.3389/fcvm.2023.1208227] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Accepted: 07/18/2023] [Indexed: 08/19/2023] Open
Abstract
Background Cardiovascular tissue engineering (CTE) is a promising technique to treat incurable cardiovascular diseases, such as myocardial infarction and ischemic cardiomyopathy. Plenty of studies related to CTE have been published in the last 30 years. However, an analysis of the research status, trends, and potential directions in this field is still lacking. The present study applies a bibliometric analysis to reveal CTE research trends and potential directions. Methods On 5 August 2022, research articles and review papers on CTE were searched from the Web of Science Core Collection with inclusion and exclusion criteria. Publication trends, research directions, and visual maps in this field were obtained using Excel (Microsoft 2009), VOSviewer, and Citespace software. Results A total of 2,273 documents from 1992 to 2022 were included in the final analysis. Publications on CTE showed an upward trend from 1992 [number of publications (Np):1] to 2021 (Np:165). The United States (Np: 916, number of citations: 152,377, H-index: 124) contributed the most publications and citations in this field. Research on CTE has a wide distribution of disciplines, led by engineering (Np: 788, number of citations: 40,563, H-index: 105). "Functional maturation" [red cluster, average published year (APY): 2018.63, 30 times], "cell-derived cardiomyocytes" (red cluster, APY: 2018.43, 46 times), "composite scaffolds" (green cluster, APY: 2018.54, 41 times), and "maturation" (red cluster, APY: 2018.17, 84 times) are the main emerging keywords in this area. Conclusion Research on CTE is a hot research topic. The United States is a dominant player in CTE research. Interdisciplinary collaboration has played a critical role in the progress of CTE. Studies on functional maturation and the development of novel biologically relevant materials and related applications will be the potential research directions in this field.
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Affiliation(s)
- Ping Lai
- Department of Cardiology, First Affiliated Hospital of Gannan Medical University, Gannan Medical University, Ganzhou, China
- Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, China
| | - Ming Sheng
- Department of Library, Gannan Medical University, Ganzhou, China
| | - Jin-hua Ye
- Department of Physiology, School of Basic Medical Sciences, Gannan Medical University, Ganzhou, China
| | - Zhi-xian Tang
- Department of Thoracic Surgery, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Shuo Hu
- Department of Heart Medical Centre, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Bei Wang
- Department of Cardiology, First Affiliated Hospital of Gannan Medical University, Gannan Medical University, Ganzhou, China
| | - Jing-lin Yuan
- Department of Cardiology, First Affiliated Hospital of Gannan Medical University, Gannan Medical University, Ganzhou, China
| | - Yi-hong Yang
- Department of Cardiology, First Affiliated Hospital of Gannan Medical University, Gannan Medical University, Ganzhou, China
| | - Yi-ming Zhong
- Department of Cardiology, First Affiliated Hospital of Gannan Medical University, Gannan Medical University, Ganzhou, China
- Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, China
| | - Yong-ling Liao
- Department of Cardiology, First Affiliated Hospital of Gannan Medical University, Gannan Medical University, Ganzhou, China
- Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, China
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28
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Zhang K, Li Y, Huang Y, Sun K. PiRNA in Cardiovascular Disease: Focus on Cardiac Remodeling and Cardiac Protection. J Cardiovasc Transl Res 2023; 16:768-777. [PMID: 37407865 DOI: 10.1007/s12265-023-10353-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2022] [Accepted: 01/08/2023] [Indexed: 07/07/2023]
Abstract
Cardiovascular diseases (CVDs) are common causes of death, which take about 18.6 million lives worldwide every year. Currently, exploring strategies that delay ventricular remodeling, reduce cardiomyocyte death, and promote cardiomyocyte regeneration has been the hotspot and difficulty of the ischemic heart disease (IHD) research field. Previous studies indicate that piwi-interacting RNA (piRNA) plays a vital role in the occurrence and development of cardiac remodeling and may offer novel therapeutic strategies for cardiac repair. The best-known biological function of piRNA is to silence transposons in cells. In the cardiovascular system, piRNA is known to participate in cardiac progenitor cell proliferation, AKT pathway regulation, and cardiac remodeling and decompensation. In this review, we systematically discuss the research progress on piRNA in CVDs, especially the mechanism of cardiac remodeling and the potential functions in cardiac protection, which provides new insights for the progress and treatment of cardiovascular diseases. Piwi-interacting RNA (piRNA) is one of the noncoding RNAs, with the best -known biological function to silence transposons in cells. Now piRNA is found to participate in cardiac progenitor cell proliferation, AKT pathway regulation, cardiac remodeling and decompensation, which implies the potential of piRNA in the diagnosis and treatment of cardiovascular diseases. Over expression of piRNA could promote cardiac apoptosis and cardiac hypertrophy, thus targeted therapy which inhibits expression of associated piRNA may reduce cardiac remodeling and reduce inflammation caused by necrotic cardiomyocytes. PiRNA is also speculated to participate in the proliferation of cardiac progenitor cells, implying the potential to induce cardiac regeneration th erapy, which provides new insights for treatment of cardiovascular diseases. At present, the treatment strategy of cardiac remodeling emphasizes the control of risk factors, prevention of disease progression and individualized treatment. With further studies in mechanism of piRNA, potential therapies above may come true and more therapies in cardiovascular diseases may be found.
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Affiliation(s)
- Kaiyu Zhang
- Department of Cardiology, Gusu School, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Nanjing Medical University, Suzhou, 215000, Jiangsu Province, China
| | - Yafei Li
- Department of Cardiology, Gusu School, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Nanjing Medical University, Suzhou, 215000, Jiangsu Province, China
| | - Ying Huang
- Central Laboratory, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China
| | - Kangyun Sun
- Department of Cardiology, Gusu School, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Nanjing Medical University, Suzhou, 215000, Jiangsu Province, China.
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Wang H, Guo Y, Hu Y, Zhou Y, Chen Y, Huang X, Chen J, Deng Q, Cao S, Hu B, Jiang R, Pan J, Tan T, Wang Y, Chen Y, Dong Q, Chen P, Zhou Q. Ultrasound-controlled nano oxygen carriers enhancing cell viability in 3D GelMA hydrogel for the treatment of myocardial infarction. Int J Biol Macromol 2023:125139. [PMID: 37268076 DOI: 10.1016/j.ijbiomac.2023.125139] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Revised: 05/25/2023] [Accepted: 05/26/2023] [Indexed: 06/04/2023]
Abstract
Heart failure is a critical and ultimate phase of cardiovascular ailment that leads to a considerable incidence of disability and mortality. Among various factors contributing to heart failure, myocardial infarction is one of the most frequent and significant causes, which is still difficult to manage effectively. An innovative therapeutic strategy, namely a 3D bio-printed cardiac patch, has recently emerged as a promising approach to substitute damaged cardiomyocytes in a localized infarct region. Nevertheless, the efficacy of this treatment primarily relies on the long-term viability of the transplanted cells. In this study, we aimed to construct acoustically sensitive nano oxygen carriers to improve cell survival inside the bio-3D printed patch. In this study, we initially created nanodroplets capable of phase transition triggered by ultrasound and integrated them into GelMA (Gelatin Methacryloyl) hydrogels, which were then employed for 3D bioprinting. After adding nanodroplets and ultrasonic irradiation, numerous pores appeared inside the hydrogel with improved permeability. We further encapsulated hemoglobin into nanodroplets (ND-Hb) to construct oxygen carriers. Results of in vitro experiments showed the highest cell survival within the patch of ND-Hb irradiated by the low-intensity pulsed ultrasound (LIPUS) group. The genomic analysis discovered that the increased survival of seeded cells within the patch might be related to the protection of mitochondrial function owing to the improved hypoxic state. Eventually, in vivo studies revealed that the LIPUS+ND-Hb group had improved cardiac function and increased revascularization after myocardial infarction. To summarize, our study successfully improved the permeability of the hydrogel in a non-invasive and efficient manner, facilitating the exchange of substances in the cardiac patch. Moreover, ultrasound-controlled oxygen release augmented the viability of the transplanted cells and expedited the repair of infarcted tissues.
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Affiliation(s)
- Hao Wang
- Renmin Hospital of Wuhan University, 430060 Wuhan, China
| | - Yuxin Guo
- Renmin Hospital of Wuhan University, 430060 Wuhan, China
| | - Yugang Hu
- Renmin Hospital of Wuhan University, 430060 Wuhan, China
| | - Yanxiang Zhou
- Renmin Hospital of Wuhan University, 430060 Wuhan, China
| | - Yueying Chen
- Renmin Hospital of Wuhan University, 430060 Wuhan, China
| | - Xin Huang
- Renmin Hospital of Wuhan University, 430060 Wuhan, China
| | - Jinling Chen
- Renmin Hospital of Wuhan University, 430060 Wuhan, China
| | - Qing Deng
- Renmin Hospital of Wuhan University, 430060 Wuhan, China
| | - Sheng Cao
- Renmin Hospital of Wuhan University, 430060 Wuhan, China
| | - Bo Hu
- Renmin Hospital of Wuhan University, 430060 Wuhan, China
| | - Riyue Jiang
- Renmin Hospital of Wuhan University, 430060 Wuhan, China
| | - Juhong Pan
- Renmin Hospital of Wuhan University, 430060 Wuhan, China
| | - Tuantuan Tan
- Renmin Hospital of Wuhan University, 430060 Wuhan, China
| | - Yijia Wang
- Renmin Hospital of Wuhan University, 430060 Wuhan, China
| | - Yun Chen
- Wuhan University School of Basic Medical Science, 430060 Wuhan, China
| | - Qi Dong
- Wuhan University School of Basic Medical Science, 430060 Wuhan, China
| | - Pu Chen
- Wuhan University School of Basic Medical Science, 430060 Wuhan, China
| | - Qing Zhou
- Renmin Hospital of Wuhan University, 430060 Wuhan, China.
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Yan X, Liu X, Zhao C, Chen GQ. Applications of synthetic biology in medical and pharmaceutical fields. Signal Transduct Target Ther 2023; 8:199. [PMID: 37169742 PMCID: PMC10173249 DOI: 10.1038/s41392-023-01440-5] [Citation(s) in RCA: 37] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2022] [Revised: 03/15/2023] [Accepted: 03/24/2023] [Indexed: 05/13/2023] Open
Abstract
Synthetic biology aims to design or assemble existing bioparts or bio-components for useful bioproperties. During the past decades, progresses have been made to build delicate biocircuits, standardized biological building blocks and to develop various genomic/metabolic engineering tools and approaches. Medical and pharmaceutical demands have also pushed the development of synthetic biology, including integration of heterologous pathways into designer cells to efficiently produce medical agents, enhanced yields of natural products in cell growth media to equal or higher than that of the extracts from plants or fungi, constructions of novel genetic circuits for tumor targeting, controllable releases of therapeutic agents in response to specific biomarkers to fight diseases such as diabetes and cancers. Besides, new strategies are developed to treat complex immune diseases, infectious diseases and metabolic disorders that are hard to cure via traditional approaches. In general, synthetic biology brings new capabilities to medical and pharmaceutical researches. This review summarizes the timeline of synthetic biology developments, the past and present of synthetic biology for microbial productions of pharmaceutics, engineered cells equipped with synthetic DNA circuits for diagnosis and therapies, live and auto-assemblied biomaterials for medical treatments, cell-free synthetic biology in medical and pharmaceutical fields, and DNA engineering approaches with potentials for biomedical applications.
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Affiliation(s)
- Xu Yan
- School of Life Sciences, Tsinghua University, 100084, Beijing, China
| | - Xu Liu
- PhaBuilder Biotech Co. Ltd., Shunyi District, Zhaoquan Ying, 101309, Beijing, China
| | - Cuihuan Zhao
- School of Life Sciences, Tsinghua University, 100084, Beijing, China
| | - Guo-Qiang Chen
- School of Life Sciences, Tsinghua University, 100084, Beijing, China.
- Center for Synthetic and Systems Biology, Tsinghua University, 100084, Beijing, China.
- MOE Key Lab for Industrial Biocatalysis, Dept Chemical Engineering, Tsinghua University, 100084, Beijing, China.
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Brlecic PE, Bonham CA, Rosengart TK, Mathison M. Direct cardiac reprogramming: A new technology for cardiac repair. J Mol Cell Cardiol 2023; 178:51-58. [PMID: 36965701 PMCID: PMC10124164 DOI: 10.1016/j.yjmcc.2023.03.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2022] [Revised: 03/03/2023] [Accepted: 03/21/2023] [Indexed: 03/27/2023]
Abstract
Cardiovascular disease is one of the leading causes of morbidity and mortality worldwide, with myocardial infarctions being amongst the deadliest manifestations. Reduced blood flow to the heart can result in the death of cardiac tissue, leaving affected patients susceptible to further complications and recurrent disease. Further, contemporary management typically involves a pharmacopeia to manage the metabolic conditions contributing to atherosclerotic and hypertensive heart disease, rather than regeneration of the damaged myocardium. With modern healthcare extending lifespan, a larger demographic will be at risk for heart disease, driving the need for novel therapeutics that surpass those currently available in efficacy. Transdifferentiation and cellular reprogramming have been looked to as potential methods for the treatment of diseases throughout the body. Specifically targeting the fibrotic cells in cardiac scar tissue as a source to be reprogrammed into induced cardiomyocytes remains an appealing option. This review aims to highlight the history of and advances in cardiac reprogramming and describe its translational potential as a treatment for cardiovascular disease.
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Affiliation(s)
- Paige E Brlecic
- Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA
| | - Clark A Bonham
- Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA
| | - Todd K Rosengart
- Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA
| | - Megumi Mathison
- Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA.
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32
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Abdolahzadeh H, Rad NK, Shpichka A, Golroo R, Rahi K, Timashev P, Hassan M, Vosough M. Progress and promise of cell sheet assisted cardiac tissue engineering in regenerative medicine. Biomed Mater 2023; 18. [PMID: 36758240 DOI: 10.1088/1748-605x/acbad4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Accepted: 02/09/2023] [Indexed: 02/11/2023]
Abstract
Cardiovascular diseases (CVDs) are the most common leading causes of premature deaths in all countries. To control the harmful side effects of CVDs on public health, it is necessary to understand the current and prospective strategies in prevention, management, and monitoring CVDs.In vitro,recapitulating of cardiac complex structure with its various cell types is a challenging topic in tissue engineering. Cardiac tissue engineering (CTE) is a multi-disciplinary strategy that has been considered as a novel alternative approach for cardiac regenerative medicine and replacement therapies. In this review, we overview various cell types and approaches in cardiac regenerative medicine. Then, the applications of cell-sheet-assisted CTE in cardiac diseases were discussed. Finally, we described how this technology can improve cardiac regeneration and function in preclinical and clinical models.
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Affiliation(s)
- Hadis Abdolahzadeh
- Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Niloofar Khoshdel Rad
- Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Anastasia Shpichka
- World-Class Research Center 'Digital Biodesign and Personalized Healthcare', Sechenov University, Moscow, Russia.,Institute for Regenerative Medicine, Sechenov University, Moscow, Russia.,Chemistry Department, Lomonosov Moscow State University, Moscow, Russia
| | - Reihaneh Golroo
- Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Kosar Rahi
- Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Peter Timashev
- World-Class Research Center 'Digital Biodesign and Personalized Healthcare', Sechenov University, Moscow, Russia.,Institute for Regenerative Medicine, Sechenov University, Moscow, Russia.,Chemistry Department, Lomonosov Moscow State University, Moscow, Russia
| | - Moustapha Hassan
- Experimental Cancer Medicine, Institution for Laboratory Medicine, Karolinska Institute, Stockholm, Sweden
| | - Massoud Vosough
- Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.,Chemistry Department, Lomonosov Moscow State University, Moscow, Russia.,Experimental Cancer Medicine, Institution for Laboratory Medicine, Karolinska Institute, Stockholm, Sweden
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33
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Fassina D, M Costa C, Bishop M, Plank G, Whitaker J, Harding SE, Niederer SA. Assessing the arrhythmogenic risk of engineered heart tissue patches through in silico application on infarcted ventricle models. Comput Biol Med 2023; 154:106550. [PMID: 36701966 DOI: 10.1016/j.compbiomed.2023.106550] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 01/02/2023] [Accepted: 01/11/2023] [Indexed: 01/15/2023]
Abstract
BACKGROUND Post myocardial infarction (MI) ventricles contain fibrotic tissue and may have disrupted electrical properties, both of which predispose to an increased risk of life-threatening arrhythmias. Application of epicardial patches obtained from human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are a potential long-term therapy to treat heart failure resulting from post MI remodelling. However, whether the introduction of these patches is anti- or pro-arrhythmic has not been studied. METHODS We studied arrhythmic risk using in silico engineered heart tissue (EHT) patch engraftment on human post-MI ventricular models. Two patient models were studied, including one with a large dense scar and one with an apparent channel of preserved viability bordered on both sides by scar. In each heart model a virtual EHT patch was introduced as a layer of viable tissue overlying the scarred area, with hiPSC-CMs electrophysiological properties. The incidence of re-entrant and sustained activation in simulations with and without EHT patches was assessed and the arrhythmia inducibility compared in the context of different EHT patch properties (conduction velocity (CV) and action potential duration (APD)). The impact of the EHT patch on the likelihood of focal ectopic impulse propagation was estimated by assessing the minimum stimulus strength and duration required to generate a propagating impulse in the scar border zone (BZ) with and without patch. RESULTS We uncovered two main mechanisms by which ventricular tachycardia (VT) risk could be either augmented or attenuated by the interaction of the patch with the tissue. In the case of isthmus-related VT, our simulations predict that EHT patches can prevent the induction of VT when the, generally longer, hiPSC-CMs APD is reduced towards more physiological values. In the case of large dense scar, we found that, an EHT patch with CV similar to the host myocardium does not promote VT, while EHT patches with lower CV increase the risk of VT, by promoting both non-sustained and sustained re-entry. Finally, our simulations indicate that electrically coupled EHT patches reduce the likelihood of propagation of focal ectopic impulses. CONCLUSIONS The introduction of EHT patches as a treatment for heart failure has the potential to augment or attenuate the risk of ventricular arrhythmias, and variations in the anatomic configuration of the substrate, the functional properties of the BZ and the electrophysiologic properties of the patch itself will determine the overall impact. Planning for delivery of this therapy will need to consider the possible impact on arrhythmia.
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Affiliation(s)
- Damiano Fassina
- School of Biomedical Engineering and Imaging Sciences, King's College London, London, UK; National Heart and Lung Institute, Imperial College London, London, UK.
| | - Caroline M Costa
- School of Biomedical Engineering and Imaging Sciences, King's College London, London, UK
| | - Martin Bishop
- School of Biomedical Engineering and Imaging Sciences, King's College London, London, UK
| | | | | | - Sian E Harding
- National Heart and Lung Institute, Imperial College London, London, UK
| | - Steven A Niederer
- School of Biomedical Engineering and Imaging Sciences, King's College London, London, UK
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Thummarati P, Laiwattanapaisal W, Nitta R, Fukuda M, Hassametto A, Kino-oka M. Recent Advances in Cell Sheet Engineering: From Fabrication to Clinical Translation. Bioengineering (Basel) 2023; 10:211. [PMID: 36829705 PMCID: PMC9952256 DOI: 10.3390/bioengineering10020211] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Revised: 01/26/2023] [Accepted: 02/01/2023] [Indexed: 02/08/2023] Open
Abstract
Cell sheet engineering, a scaffold-free tissue fabrication technique, has proven to be an important breakthrough technology in regenerative medicine. Over the past two decades, the field has developed rapidly in terms of investigating fabrication techniques and multipurpose applications in regenerative medicine and biological research. This review highlights the most important achievements in cell sheet engineering to date. We first discuss cell sheet harvesting systems, which have been introduced in temperature-responsive surfaces and other systems to overcome the limitations of conventional cell harvesting methods. In addition, we describe several techniques of cell sheet transfer for preclinical (in vitro and in vivo) and clinical trials. This review also covers cell sheet cryopreservation, which allows short- and long-term storage of cells. Subsequently, we discuss the cell sheet properties of angiogenic cytokines and vasculogenesis. Finally, we discuss updates to various applications, from biological research to clinical translation. We believe that the present review, which shows and compares fundamental technologies and recent advances in cell engineering, can potentially be helpful for new and experienced researchers to promote the further development of tissue engineering in different applications.
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Affiliation(s)
- Parichut Thummarati
- Department of Biotechnology, Graduate School of Engineering, Osaka University, Osaka 565-0871, Japan
- Biosensors and Bioanalytical Technology for Cells and Innovative Testing Device Research Unit, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand
| | - Wanida Laiwattanapaisal
- Biosensors and Bioanalytical Technology for Cells and Innovative Testing Device Research Unit, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand
| | - Rikiya Nitta
- Department of Biotechnology, Graduate School of Engineering, Osaka University, Osaka 565-0871, Japan
| | - Megumi Fukuda
- Department of Biotechnology, Graduate School of Engineering, Osaka University, Osaka 565-0871, Japan
| | - Artchaya Hassametto
- Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
| | - Masahiro Kino-oka
- Department of Biotechnology, Graduate School of Engineering, Osaka University, Osaka 565-0871, Japan
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35
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Lim J, Lee MS, Jeon J, Yang HS. Fibrinogen-based cell and spheroid sheets manipulating and delivery for mouse hindlimb ischemia. Biofabrication 2023; 15. [PMID: 36630715 DOI: 10.1088/1758-5090/acb233] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Accepted: 01/11/2023] [Indexed: 01/12/2023]
Abstract
In this research, we introduced a novel strategy for fabricating cell sheets (CSs) prepared by simply adding a fibrinogen solution to growth medium without using any synthetic polymers or chemical agents. We confirmed that the fibrinogen-based CS could be modified for target tissue regardless of size, shape, and cell types. Also, fibrinogen-based CSs were versatile and could be used to form three-dimensional (3D) CSs such as multi-layered CSs and those mimicking native blood vessels. We also prepared fibrinogen-based spheroid sheets for the treatment of ischemic disease. The fibrinogen-based spheroid sheets had much higherin vitrotubule formation and released more angiogenic factors compared to other types of platform in this research. We transplanted fibrinogen-based spheroid sheets into a mouse hindlimb ischemia model and found that fibrinogen-based spheroid sheets showed significantly improved physiological function and blood perfusion rates compared to the other types of platform in this research.
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Affiliation(s)
- Juhan Lim
- Department of Nanobiomedical Science & BK21 FOUR NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 31116, Republic of Korea
| | - Min Suk Lee
- Department of Nanobiomedical Science & BK21 FOUR NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 31116, Republic of Korea.,Medical Laser Research Center, College of Medicine, Dankook University, Cheonan 31116, Republic of Korea
| | - Jin Jeon
- Department of Nanobiomedical Science & BK21 FOUR NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 31116, Republic of Korea
| | - Hee Seok Yang
- Department of Nanobiomedical Science & BK21 FOUR NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 31116, Republic of Korea.,Bio-Medical Engineering Research Center, Dankook University, Cheonan 31116, Republic of Korea
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36
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Azizidoost S, Farzaneh M. MicroRNAs as a Novel Player for Differentiation of Mesenchymal Stem Cells into Cardiomyocytes. Curr Stem Cell Res Ther 2023; 18:27-34. [PMID: 35466882 DOI: 10.2174/1574888x17666220422094150] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Revised: 02/14/2022] [Accepted: 03/02/2022] [Indexed: 11/22/2022]
Abstract
Cardiovascular disease (CVD) is defined as a class of disorders affecting the heart and blood vessels. Cardiomyocytes and endothelial cells play important roles in cardiac regeneration and heart repair. However, the proliferating capacity of cardiomyocytes is limited. To overcome this issue, mesenchymal stem cells (MSCs) have emerged as an alternative strategy for CVD therapy. MSCs can proliferate and differentiate (or trans-differentiate) into cardiomyocytes. Several in vitro and in vivo differentiation protocols have been used to obtain MSCs-derived cardiomyocytes. It was recently investigated that microRNAs (miRNAs) by targeting several signaling pathways, including STAT3, Wnt/β-catenin, Notch, and TBX5, play a crucial role in regulating cardiomyocytes' differentiation of MSCs. In this review, we focused on the role of miRNAs in the differentiation of MSCs into cardiomyocytes.
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Affiliation(s)
- Shirin Azizidoost
- Atherosclerosis Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Maryam Farzaneh
- Fertility, Infertility and Perinatology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.,Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
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Wang J, Guo S, Xu X, Zhang C. 1,25-Dihydroxyvitamin D3: A Positive Factor for the Osteogenic Differentiation of hPDLSCs and for the Tissue Regenerative Activity of Cell Sheets. Cell Transplant 2023; 32:9636897231202541. [PMID: 37798942 PMCID: PMC10557410 DOI: 10.1177/09636897231202541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Revised: 08/12/2023] [Accepted: 09/05/2023] [Indexed: 10/07/2023] Open
Abstract
This study aims to investigate the effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2VitD3) on osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) and the activity of hPDLSC sheets and the differences in the tissue regeneration activity of hPDLSC sheets on tooth root fragment treated by different methods. Healthy caries-free premolars were collected. The hPDLSCs were obtained by enzymatic digestion. Surface markers of stem cells were analyzed by flow cytometry and the multidirectional differentiation ability of hPDLSCs was detected. During the osteogenic differentiation of hPDLSCs, 1,25(OH)2VitD3 was added and the effect of 1,25(OH)2VitD3 on osteogenic differentiation of hPDLSCs was assessed using Western blotting, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay, cell staining, and immunofluorescence. After hPDLSC sheets were prepared, histology and immunofluorescence analysis of the effect of 1,25(OH)2VitD3 on sheet activity were performed. In addition, root fragments were prepared and treated with scaling, 24% EDTA (ethylenediamide tetraacetic acid), and Er,Cr:YSGG lasers, respectively, and the tissue regeneration activity of hPDLSC sheets on different root fragments were observed. 1,25(OH)2VitD3 promoted the high gene and protein expressions of osteogenic markers ALP (alkaline phosphatase), Runx2, and OPN (osteopontin antibody) in hPDLSCs, along with enhanced ALP activity and staining, alizarin red staining, and immunofluorescence staining, indicating that the osteogenic differentiation ability of hPDLSCs was improved. Extracellular matrix secretion was increased in hPDLSC sheets, along with the positive expressions of the protein markers fibronectin and collagen I, suggesting that 1,25(OH)2VitD3 could enhance these effects. In addition, the root fragments treated by Er,Cr:YSGG laser were more suitable for the attachment and regeneration of hPDLSC sheets, demonstrating that 1,25(OH)2VitD3 could improve the tissue regeneration performance of these sheets. 1,25(OH)2VitD3 can promote osteogenic differentiation of hPDLSCs and thus plays an active role in hPDLSC sheet formation and tissue regeneration. In addition, the Er,Cr:YSGG laser can be used as the recommended treatment method for the root surface regenerated by hPDLSCs.
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Affiliation(s)
- Jingjiao Wang
- Department of Stomatology, General Hospital of Ningxia Medical University, Yinchuan, China
| | - Songlin Guo
- Institute of Stem Cells, General Hospital of Ningxia Medical University, Yinchuan, China
| | - Xiaobo Xu
- School of Stomatology, Ningxia Medical University, Yinchuan, China
| | - Chenglei Zhang
- Medical Laboratory, General Hospital of Ningxia Medical University, Yinchuan, China
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38
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Duman BO, Sariboyaci AE, Karaoz E. Bio-engineering of 3-D cell sheets for diabetic rats: Interaction between mesenchymal stem cells and beta cells in functional islet regeneration system. Tissue Cell 2022; 79:101919. [DOI: 10.1016/j.tice.2022.101919] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Revised: 07/22/2022] [Accepted: 09/03/2022] [Indexed: 11/15/2022]
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Advances in Cardiac Tissue Engineering. Bioengineering (Basel) 2022; 9:bioengineering9110696. [DOI: 10.3390/bioengineering9110696] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 11/09/2022] [Accepted: 11/15/2022] [Indexed: 11/17/2022] Open
Abstract
Tissue engineering has paved the way for the development of artificial human cardiac muscle patches (hCMPs) and cardiac tissue analogs, especially for treating Myocardial infarction (MI), often by increasing its regenerative abilities. Low engraftment rates, insufficient clinical application scalability, and the creation of a functional vascular system remain obstacles to hCMP implementation in clinical settings. This paper will address some of these challenges, present a broad variety of heart cell types and sources that can be applied to hCMP biomanufacturing, and describe some new innovative methods for engineering such treatments. It is also important to note the injection/transplantation of cells in cardiac tissue engineering.
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40
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Smart surface-based cell sheet engineering for regenerative medicine. TRENDS IN CHEMISTRY 2022. [DOI: 10.1016/j.trechm.2022.11.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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41
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Tsujimura M, Kusamori K, Takamura K, Ito T, Kaya T, Shimizu K, Konishi S, Nishikawa M. Quality evaluation of cell spheroids for transplantation by monitoring oxygen consumption using an on-chip electrochemical device. BIOTECHNOLOGY REPORTS (AMSTERDAM, NETHERLANDS) 2022; 36:e00766. [PMID: 36245695 PMCID: PMC9562952 DOI: 10.1016/j.btre.2022.e00766] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Revised: 09/19/2022] [Accepted: 10/01/2022] [Indexed: 11/18/2022]
Abstract
Three-dimensional cell spheroids are superior cell-administration form for cell-based therapy which generally exhibit superior functionality and long-term survival after transplantation. Here, we nondestructively measured the oxygen consumption rate of cell spheroids using an on-chip electrochemical device (OECD) and examined whether this rate can be used as a marker to estimate the quality of cell spheroids. Cell spheroids containing NanoLuc luciferase-expressing mouse mesenchymal stem cell line C3H10T1/2 (C3H10T1/2/Nluc) were prepared. Spheroids of high or low quality were prepared by altering the medium change frequency. After transplantation into mice, the high-quality C3H10T1/2/Nluc spheroids exhibited a higher survival rate than the low-quality ones. The oxygen consumption rate of the high-quality C3H10T1/2/Nluc spheroids was maintained at high levels, whereas that of the low-quality spheroids decreased with time. These results indicate that OECD-based measurement of the oxygen consumption rate can be used to estimate the quality of cell spheroids without destructive analysis of the spheroids.
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Affiliation(s)
- Mari Tsujimura
- Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan
| | - Kosuke Kusamori
- Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan
- Corresponding author.
| | - Kodai Takamura
- Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan
| | - Temmei Ito
- KONICA MINOLTA, INC., No.1 Sakura-machi, Hino-shi, Tokyo, 191-8511, Japan
| | - Takatoshi Kaya
- KONICA MINOLTA, INC., No.1 Sakura-machi, Hino-shi, Tokyo, 191-8511, Japan
| | - Kazunori Shimizu
- Department of Biomolecular Engineering, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi, 464-8603, Japan
| | - Satoshi Konishi
- Department of Mechanical Engineering, Graduate School of Science and Engineering, Ritsumeikan University, 1-1-1 Noji-higashi, Kusatsu, Shiga, 525-8577, Japan
| | - Makiya Nishikawa
- Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan
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Feng H, Liu Q, Deng Z, Li H, Zhang H, Song J, Liu X, Liu J, Wen B, Wang T. Human umbilical cord mesenchymal stem cells ameliorate erectile dysfunction in rats with diabetes mellitus through the attenuation of ferroptosis. Stem Cell Res Ther 2022; 13:450. [PMID: 36064453 PMCID: PMC9444126 DOI: 10.1186/s13287-022-03147-w] [Citation(s) in RCA: 54] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Accepted: 08/18/2022] [Indexed: 11/15/2022] Open
Abstract
Background Erectile dysfunction (ED), as one of the most prevalent consequences in male diabetic patients, has a serious impact on men's physical and mental health, and the treatment effect of diabetic mellitus erectile dysfunction (DMED) is often worse. Therefore, the development of a novel therapeutic approach is urgent. As stem cells with high differentiation potential, human umbilical cord mesenchymal stem cells (HUCMSCs) have been widely used in the treatment of diseases in other systems, and are expected to be a promising strategy for the treatment of DMED. In this study, we investigated the role of HUCMSCs in managing erectile function in rat models of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) and compared the effects of two different injection methods. Methods T1DM and T2DM ED rats were given labelled HUCMSCs by corpus cavernosum injection and tail vein injection, respectively. ICP and MAP were monitored simultaneously by electrical stimulation four weeks after injection to indicate the erectile function of rats. To track the development and colonisation capabilities of stem cells, we performed EdU assay with penile tissue. The histological changes of the penis were observed by hematoxylin–eosin staining, and Masson’s trichrome staining was conducted to evaluate the smooth muscle content and the degree of fibrosis in the rat penis. Then, we employed specific kits to measure the level of NO, cGMP, MDA, SOD and Fe in penis. Electron transmission microscopy was implemented to observe morphology of mitochondria. Besides, western blot and immunofluorescence staining were performed to demonstrate the expression of ferroptosis-related genes. Results We found that HUCMSCs improved erectile function in T1DM and T2DM ED rats, with no difference in efficacy between corpus cavernosum injection and tail vein injection. The EdU assay revealed that only a tiny percentage of HUCMSCs colonised the corpus cavernosum, while smooth muscle in the penis expanded and collagen decreased following HUCMSC injection. Moreover, the levels of oxidative stress in the penis of the rats given HUCMSCs were dramatically reduced, as was the tissue iron content. HUCMSCs normalised mitochondrial morphology within corpus cavernosum smooth muscle cells (CCSMCs), which were characteristically altered by high glucose. Furthermore, the expression of ferroptosis inhibitory genes SLC7A11 and GPX4 was obviously elevated in CCSMCs after stem cell management, but the abundances of ACSL4, LPCAT3 and ALOX15 showed the polar opposite tendency. Conclusions HUCMSCs can effectively and safely alleviate erectile dysfunction in T1DM and T2DM ED rats, while restoring erectile function by attenuating diabetes-induced ferroptosis in CCSMCs. Additionally, this study provides significant evidence for the development of HUCMSCs as a viable therapeutic strategy for DMED. Supplementary Information The online version contains supplementary material available at 10.1186/s13287-022-03147-w.
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Affiliation(s)
- Huan Feng
- Department of Urology, Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Qi Liu
- Department of Urology, Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen, Guangdong, China
| | - Zhiyao Deng
- Department of Urology, Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.,Shenzhen Huazhong University of Science and Technology Research Institute, Shenzhen, Guangdong, China
| | - Hao Li
- Department of Urology, Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Huajie Zhang
- Department of Urology, Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen, Guangdong, China
| | - Jingyu Song
- Department of Urology, Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Xiaming Liu
- Department of Urology, Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Jihong Liu
- Department of Urology, Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Bo Wen
- Department of Urology, Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen, Guangdong, China.
| | - Tao Wang
- Department of Urology, Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. .,Shenzhen Huazhong University of Science and Technology Research Institute, Shenzhen, Guangdong, China.
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Yuan SM, Yang XT, Zhang SY, Tian WD, Yang B. Therapeutic potential of dental pulp stem cells and their derivatives: Insights from basic research toward clinical applications. World J Stem Cells 2022; 14:435-452. [PMID: 36157522 PMCID: PMC9350620 DOI: 10.4252/wjsc.v14.i7.435] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Revised: 05/25/2022] [Accepted: 06/20/2022] [Indexed: 02/06/2023] Open
Abstract
For more than 20 years, researchers have isolated and identified postnatal dental pulp stem cells (DPSCs) from different teeth, including natal teeth, exfoliated deciduous teeth, healthy teeth, and diseased teeth. Their mesenchymal stem cell (MSC)-like immunophenotypic characteristics, high proliferation rate, potential for multidirectional differentiation and biological features were demonstrated to be superior to those of bone marrow MSCs. In addition, several main application forms of DPSCs and their derivatives have been investigated, including stem cell injections, modified stem cells, stem cell sheets and stem cell spheroids. In vitro and in vivo administration of DPSCs and their derivatives exhibited beneficial effects in various disease models of different tissues and organs. Therefore, DPSCs and their derivatives are regarded as excellent candidates for stem cell-based tissue regeneration. In this review, we aim to provide an overview of the potential application of DPSCs and their derivatives in the field of regenerative medicine. We describe the similarities and differences of DPSCs isolated from donors of different ages and health conditions. The methodologies for therapeutic administration of DPSCs and their derivatives are introduced, including single injections and the transplantation of the cells with a support, as cell sheets, or as cell spheroids. We also summarize the underlying mechanisms of the regenerative potential of DPSCs.
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Affiliation(s)
- Sheng-Meng Yuan
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Engineering Research Center of Oral Translational Medicine, National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
- Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Xue-Ting Yang
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Engineering Research Center of Oral Translational Medicine, National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
- Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Si-Yuan Zhang
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Engineering Research Center of Oral Translational Medicine, National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Wei-Dong Tian
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Engineering Research Center of Oral Translational Medicine, National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
- Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Bo Yang
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Engineering Research Center of Oral Translational Medicine, National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
- Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
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Liu J, Liang X, Li M, Lin F, Ma X, Xin Y, Meng Q, Zhuang R, Zhang Q, Han W, Gao L, He Z, Zhou X, Liu Z. Intramyocardial injected human umbilical cord-derived mesenchymal stem cells (HucMSCs) contribute to the recovery of cardiac function and the migration of CD4 + T cells into the infarcted heart via CCL5/CCR5 signaling. Stem Cell Res Ther 2022; 13:247. [PMID: 35690805 PMCID: PMC9188247 DOI: 10.1186/s13287-022-02914-z] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Accepted: 05/25/2022] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Human umbilical cord-derived mesenchymal stem cells (HucMSCs) have been recognized as a promising cell for treating myocardial infarction (MI). Inflammatory response post MI is critical in determining the cardiac function and subsequent adverse left ventricular remodeling. However, the local inflammatory effect of HucMSCs after intramyocardial injection in murine remains unclear. METHODS HucMSCs were cultured and transplanted into the mice after MI surgery. Cardiac function of mice were analyzed among MI-N.S, MI-HucMSC and MI-HucMSC-C-C Motif Chemokine receptor 5 (CCR5) antagonist groups, and angiogenesis, fibrosis and hypertrophy, and immune cells infiltration of murine hearts were evaluated between MI-N.S and MI-HucMSC groups. We detected the expression of inflammatory cytokines and their effects on CD4+ T cells migration. RESULTS HucMSCs treatment can significantly improve the cardiac function and some cells can survive at least 28 days after MI. Intramyocardial administration of HucMSCs also improved angiogenesis and alleviated cardiac fibrosis and hypertrophy. Moreover, we found the much higher numbers of CD4+ T cells and CD4+FoxP3+ regulatory T cells (Tregs) in the heart with HucMSCs than that with N.S treatment on day 7 post MI. In addition, the protein level of C-C Motif Chemokine Ligand 5 (CCL5) greatly increased in HucMSCs treated heart compared to MI-N.S group. In vitro, HucMSCs inhibited CD4+ T cells migration and addition of CCL5 antibody or CCR5 antagonist significantly reversed this effect. In vivo results further showed that addition of CCR5 antagonist can reduce the cardioprotective effect of HucMSCs administration on day 7 post MI injury. CONCLUSION These findings indicated that HucMSCs contributed to cardiac functional recovery and attenuated cardiac remodeling post MI. Intramyocardial injection of HucMSCs upregulated the CD4+FoxP3+ Tregs and contributed to the migration of CD4+ T cells into the injured heart via CCL5/CCR5 pathway.
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Affiliation(s)
- Jing Liu
- Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Rd, Pudong, Shanghai, 200120, People's Republic of China
- Department of Burn and Plastic Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, People's Republic of China
| | - Xiaoting Liang
- Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Rd, Pudong, Shanghai, 200120, People's Republic of China
- Institute for Regenerative Medicine, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, 200120, People's Republic of China
| | - Mimi Li
- Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Rd, Pudong, Shanghai, 200120, People's Republic of China
- Shanghai Heart Failure Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, People's Republic of China
| | - Fang Lin
- Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Rd, Pudong, Shanghai, 200120, People's Republic of China
- Shanghai Heart Failure Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, People's Republic of China
| | - Xiaoxue Ma
- Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Rd, Pudong, Shanghai, 200120, People's Republic of China
- Shanghai Heart Failure Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, People's Republic of China
| | - Yuanfeng Xin
- Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Rd, Pudong, Shanghai, 200120, People's Republic of China
- Department of Cardiovascular Surgery, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Rd, Pudong, Shanghai, 200120, People's Republic of China
| | - Qingshu Meng
- Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Rd, Pudong, Shanghai, 200120, People's Republic of China
- Shanghai Heart Failure Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, People's Republic of China
| | - Rulin Zhuang
- Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Rd, Pudong, Shanghai, 200120, People's Republic of China
- Department of Cardiovascular Surgery, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Rd, Pudong, Shanghai, 200120, People's Republic of China
| | - Qingliu Zhang
- Department of Heart Failure, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, People's Republic of China
- Shanghai Institute of Stem Cell Research and Clinical Translation, Shanghai, 200120, People's Republic of China
| | - Wei Han
- Department of Heart Failure, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, People's Republic of China
- Shanghai Institute of Stem Cell Research and Clinical Translation, Shanghai, 200120, People's Republic of China
| | - Ling Gao
- Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200123, People's Republic of China
| | - Zhiying He
- Institute for Regenerative Medicine, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, 200120, People's Republic of China
- Shanghai Institute of Stem Cell Research and Clinical Translation, Shanghai, 200120, People's Republic of China
- Shanghai Engineering Research Center of Stem Cells Translational Medicine, Shanghai, 200335, People's Republic of China
| | - Xiaohui Zhou
- Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Rd, Pudong, Shanghai, 200120, People's Republic of China.
- Shanghai Heart Failure Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, People's Republic of China.
| | - Zhongmin Liu
- Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Rd, Pudong, Shanghai, 200120, People's Republic of China.
- Shanghai Heart Failure Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, People's Republic of China.
- Department of Cardiovascular Surgery, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Rd, Pudong, Shanghai, 200120, People's Republic of China.
- Shanghai Institute of Stem Cell Research and Clinical Translation, Shanghai, 200120, People's Republic of China.
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Ullah A, Hoang-Trong MT, Lederer WJ, Winslow RL, Jafri MS. Critical Requirements for the Initiation of a Cardiac Arrhythmia in Rat Ventricle: How Many Myocytes? Cells 2022; 11:cells11121878. [PMID: 35741007 PMCID: PMC9221049 DOI: 10.3390/cells11121878] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Revised: 06/03/2022] [Accepted: 06/07/2022] [Indexed: 11/16/2022] Open
Abstract
Cardiovascular disease is the leading cause of death worldwide due in a large part to arrhythmia. In order to understand how calcium dynamics play a role in arrhythmogenesis, normal and dysfunctional Ca2+ signaling in a subcellular, cellular, and tissued level is examined using cardiac ventricular myocytes at a high temporal and spatial resolution using multiscale computational modeling. Ca2+ sparks underlie normal excitation-contraction coupling. However, under pathological conditions, Ca2+ sparks can combine to form Ca2+ waves. These propagating elevations of (Ca2+)i can activate an inward Na+-Ca2+ exchanger current (INCX) that contributes to early after-depolarization (EADs) and delayed after-depolarizations (DADs). However, how cellular currents lead to full depolarization of the myocardium and how they initiate extra systoles is still not fully understood. This study explores how many myocytes must be entrained to initiate arrhythmogenic depolarizations in biophysically detailed computational models. The model presented here suggests that only a small number of myocytes must activate in order to trigger an arrhythmogenic propagating action potential. These conditions were examined in 1-D, 2-D, and 3-D considering heart geometry. The depolarization of only a few hundred ventricular myocytes is required to trigger an ectopic depolarization. The number decreases under disease conditions such as heart failure. Furthermore, in geometrically restricted parts of the heart such as the thin muscle strands found in the trabeculae and papillary muscle, the number of cells needed to trigger a propagating depolarization falls even further to less than ten myocytes.
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Affiliation(s)
- Aman Ullah
- School of Systems Biology, Krasnow Institute for Advanced Study, George Mason University, Fairfax, VA 22030, USA; (A.U.); (M.T.H.-T.)
| | - Minh Tuan Hoang-Trong
- School of Systems Biology, Krasnow Institute for Advanced Study, George Mason University, Fairfax, VA 22030, USA; (A.U.); (M.T.H.-T.)
| | - William Jonathan Lederer
- Biomedical Engineering and Technology, University of Maryland School of Medicine, Baltimore, MD 21201, USA;
| | - Raimond L. Winslow
- Institute for Computational Medicine and Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, MD 20218, USA;
- The Roux Institute, Northeastern University, Portland, ME 04102, USA
| | - Mohsin Saleet Jafri
- School of Systems Biology, Krasnow Institute for Advanced Study, George Mason University, Fairfax, VA 22030, USA; (A.U.); (M.T.H.-T.)
- Biomedical Engineering and Technology, University of Maryland School of Medicine, Baltimore, MD 21201, USA;
- Institute for Computational Medicine and Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, MD 20218, USA;
- Correspondence: ; Tel.: +1-703-993-8420
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Tannenbaum SE, Reubinoff BE. Advances in hPSC expansion towards therapeutic entities: A review. Cell Prolif 2022; 55:e13247. [PMID: 35638399 PMCID: PMC9357360 DOI: 10.1111/cpr.13247] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Revised: 04/12/2022] [Accepted: 04/18/2022] [Indexed: 12/24/2022] Open
Abstract
For use in regenerative medicine, large‐scale manufacturing of human pluripotent stem cells (hPSCs) under current good manufacturing practice (cGMPs) is required. Much progress has been made since culturing under static two‐dimensional (2D) conditions on feeders, including feeder‐free cultures, conditioned and xeno‐free media, and three‐dimensional (3D) dynamic suspension expansion. With the advent of horizontal‐blade and vertical‐wheel bioreactors, scale‐out for large‐scale production of differentiated hPSCs became possible; control of aggregate size, shear stress, fluid hydrodynamics, batch‐feeding strategies, and other process parameters became a reality. Moving from substantially manipulated processes (i.e., 2D) to more automated ones allows easer compliance to current good manufacturing practices (cGMPs), and thus easier regulatory approval. Here, we review the current advances in the field of hPSC culturing, advantages, and challenges in bioreactor use, and regulatory areas of concern with respect to these advances. Manufacturing trends to reduce risk and streamline large‐scale manufacturing will bring about easier, faster regulatory approval for clinical applications.
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Affiliation(s)
- Shelly E Tannenbaum
- The Hadassah Human Embryonic Stem Cell Research Center, The Goldyne Savad Institute of Gene Therapy, Hadassah Hebrew University Medical Center, Jerusalem, Israel
| | - Benjamin E Reubinoff
- The Hadassah Human Embryonic Stem Cell Research Center, The Goldyne Savad Institute of Gene Therapy, Hadassah Hebrew University Medical Center, Jerusalem, Israel.,Department of Obstetrics and Gynecology, Hadassah Hebrew University Medical Center, Jerusalem, Israel
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Uemura L, Baggio Simeoni R, Bispo Machado Júnior PA, Gavazzoni Blume G, Kremer Gamba L, Sgarbossa Tonial M, Baggio Simeoni PR, Stadler Tasca Ribeiro V, Silvestre R, de Carvalho KAT, Napimoga MH, Cesar Francisco J, Guarita-Souza LC. Autologous Bone Marrow Mononuclear Cells (BMMC)-Associated Anti-Inflammatory Nanoparticles for Cardiac Repair after Myocardial Infarction. J Funct Biomater 2022; 13:jfb13020059. [PMID: 35645267 PMCID: PMC9149818 DOI: 10.3390/jfb13020059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Revised: 05/04/2022] [Accepted: 05/10/2022] [Indexed: 12/10/2022] Open
Abstract
To investigate the effect of transplantation of stem cells from the bone marrow mononuclear cells (BMMC) associated with 15d-PGJ2-loaded nanoparticles in a rat model of chronic MI. Chronic myocardial infarction (MI) was induced by the ligation of the left anterior descending artery in 40 male Wistar rats. After surgery, we transplanted bone marrow associated with 15d-PGJ2-loaded nanoparticle by intramyocardial injection (106 cells/per injection) seven days post-MI. Myocardial infarction was confirmed by echocardiography, and histological analyses of infarct morphology, gap junctions, and angiogenesis were obtained. Our results from immunohistochemical analyses demonstrated the presence of angiogenesis identified in the transplanted region and that there was significant expression of connexin-43 gap junctions, showing a more effective electrical and mechanical integration of the host myocardium. This study suggests that the application of nanoparticle technology in the prevention and treatment of MI is an emerging field and can be a strategy for cardiac repair.
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Affiliation(s)
- Laercio Uemura
- Experimental Laboratory of Institute of Biological and Health Sciences, Pontifícia Universidade Católica do Paraná (PUCPR), 1555 Imaculada Conceição Street, Curitiba 80215-901, Brazil; (L.U.); (P.A.B.M.J.); (G.G.B.); (L.K.G.); (M.S.T.); (P.R.B.S.); (V.S.T.R.); (J.C.F.); (L.C.G.-S.)
| | - Rossana Baggio Simeoni
- Experimental Laboratory of Institute of Biological and Health Sciences, Pontifícia Universidade Católica do Paraná (PUCPR), 1555 Imaculada Conceição Street, Curitiba 80215-901, Brazil; (L.U.); (P.A.B.M.J.); (G.G.B.); (L.K.G.); (M.S.T.); (P.R.B.S.); (V.S.T.R.); (J.C.F.); (L.C.G.-S.)
- Correspondence: ; Tel.: +55-41-988213440
| | - Paulo André Bispo Machado Júnior
- Experimental Laboratory of Institute of Biological and Health Sciences, Pontifícia Universidade Católica do Paraná (PUCPR), 1555 Imaculada Conceição Street, Curitiba 80215-901, Brazil; (L.U.); (P.A.B.M.J.); (G.G.B.); (L.K.G.); (M.S.T.); (P.R.B.S.); (V.S.T.R.); (J.C.F.); (L.C.G.-S.)
| | - Gustavo Gavazzoni Blume
- Experimental Laboratory of Institute of Biological and Health Sciences, Pontifícia Universidade Católica do Paraná (PUCPR), 1555 Imaculada Conceição Street, Curitiba 80215-901, Brazil; (L.U.); (P.A.B.M.J.); (G.G.B.); (L.K.G.); (M.S.T.); (P.R.B.S.); (V.S.T.R.); (J.C.F.); (L.C.G.-S.)
| | - Luize Kremer Gamba
- Experimental Laboratory of Institute of Biological and Health Sciences, Pontifícia Universidade Católica do Paraná (PUCPR), 1555 Imaculada Conceição Street, Curitiba 80215-901, Brazil; (L.U.); (P.A.B.M.J.); (G.G.B.); (L.K.G.); (M.S.T.); (P.R.B.S.); (V.S.T.R.); (J.C.F.); (L.C.G.-S.)
| | - Murilo Sgarbossa Tonial
- Experimental Laboratory of Institute of Biological and Health Sciences, Pontifícia Universidade Católica do Paraná (PUCPR), 1555 Imaculada Conceição Street, Curitiba 80215-901, Brazil; (L.U.); (P.A.B.M.J.); (G.G.B.); (L.K.G.); (M.S.T.); (P.R.B.S.); (V.S.T.R.); (J.C.F.); (L.C.G.-S.)
| | - Paulo Ricardo Baggio Simeoni
- Experimental Laboratory of Institute of Biological and Health Sciences, Pontifícia Universidade Católica do Paraná (PUCPR), 1555 Imaculada Conceição Street, Curitiba 80215-901, Brazil; (L.U.); (P.A.B.M.J.); (G.G.B.); (L.K.G.); (M.S.T.); (P.R.B.S.); (V.S.T.R.); (J.C.F.); (L.C.G.-S.)
| | - Victoria Stadler Tasca Ribeiro
- Experimental Laboratory of Institute of Biological and Health Sciences, Pontifícia Universidade Católica do Paraná (PUCPR), 1555 Imaculada Conceição Street, Curitiba 80215-901, Brazil; (L.U.); (P.A.B.M.J.); (G.G.B.); (L.K.G.); (M.S.T.); (P.R.B.S.); (V.S.T.R.); (J.C.F.); (L.C.G.-S.)
| | - Rodrigo Silvestre
- Instituto de Radiologia (InRad), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05508-070, Brazil;
| | - Katherine Athayde Teixeira de Carvalho
- Cell Therapy and Biotechnology in Regenerative Medicine Department, The Pelé Pequeno Príncipe Institute, Child and Adolescent Health Research & Pequeno Príncipe Faculties, 1632 Silva Jardim Avenue, Curitiba 80240-020, Brazil;
| | - Marcelo Henrique Napimoga
- Institute and Research Center São Leopoldo Mandic, São Leopoldo Mandic, Faculty–SLMANDIC, Campinas, São Paulo 13045-775, Brazil;
| | - Júlio Cesar Francisco
- Experimental Laboratory of Institute of Biological and Health Sciences, Pontifícia Universidade Católica do Paraná (PUCPR), 1555 Imaculada Conceição Street, Curitiba 80215-901, Brazil; (L.U.); (P.A.B.M.J.); (G.G.B.); (L.K.G.); (M.S.T.); (P.R.B.S.); (V.S.T.R.); (J.C.F.); (L.C.G.-S.)
| | - Luiz Cesar Guarita-Souza
- Experimental Laboratory of Institute of Biological and Health Sciences, Pontifícia Universidade Católica do Paraná (PUCPR), 1555 Imaculada Conceição Street, Curitiba 80215-901, Brazil; (L.U.); (P.A.B.M.J.); (G.G.B.); (L.K.G.); (M.S.T.); (P.R.B.S.); (V.S.T.R.); (J.C.F.); (L.C.G.-S.)
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An Overview of the Molecular Mechanisms Associated with Myocardial Ischemic Injury: State of the Art and Translational Perspectives. Cells 2022; 11:cells11071165. [PMID: 35406729 PMCID: PMC8998015 DOI: 10.3390/cells11071165] [Citation(s) in RCA: 51] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Revised: 03/22/2022] [Accepted: 03/24/2022] [Indexed: 02/06/2023] Open
Abstract
Cardiovascular disease is the leading cause of death in western countries. Among cardiovascular diseases, myocardial infarction represents a life-threatening condition predisposing to the development of heart failure. In recent decades, much effort has been invested in studying the molecular mechanisms underlying the development and progression of ischemia/reperfusion (I/R) injury and post-ischemic cardiac remodeling. These mechanisms include metabolic alterations, ROS overproduction, inflammation, autophagy deregulation and mitochondrial dysfunction. This review article discusses the most recent evidence regarding the molecular basis of myocardial ischemic injury and the new potential therapeutic interventions for boosting cardioprotection and attenuating cardiac remodeling.
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Ando Y, Okeyo KO, Adachi T. Pluripotency state of mouse ES cells determines their contribution to self-organized layer formation by mesh closure on microstructured adhesion-limiting substrates. Biochem Biophys Res Commun 2022; 590:97-102. [PMID: 34973536 DOI: 10.1016/j.bbrc.2021.12.066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Accepted: 12/18/2021] [Indexed: 11/02/2022]
Abstract
Assembly of pluripotent stem cells to initiate self-organized tissue formation on engineered scaffolds is an important process in stem cell engineering. Pluripotent stem cells are known to exist in diverse pluripotency states, with heterogeneous subpopulations exhibiting differential gene expression levels, but how such diverse pluripotency states orchestrate tissue formation is still an unrevealed question. In this study, using microstructured adhesion-limiting substrates, we aimed to clarify the contribution to self-organized layer formation by mouse embryonic stem cells in different pluripotency states: ground and naïve state. We found that while ground state cells as well as sorted REX1-high expression cells formed discontinuous cell layers with limited lateral spread, naïve state cells could successfully self-organize to form a continuous layer by progressive mesh closure within 3 days. Using sequential immunofluorescence microscopy to examine the mesh closure process, we found that KRT8+ cells were particularly localized around unfilled holes, occasionally bridging the holes in a manner suggestive of their role in the closure process. These results highlight that compared with ground state cells, naïve state cells possess a higher capability to contribute to self-organized layer formation by mesh closure. Thus, this study provides insights with implications for the application of stem cells in scaffold-based tissue engineering.
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Affiliation(s)
- Yuta Ando
- Department of Micro Engineering, Graduate School of Engineering, Kyoto University, Kyoto Daigaku-katsura, Nishikyo-ku, Kyoto, 615-8530, Japan; Institute for Frontier Life and Medical Sciences, Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Kennedy Omondi Okeyo
- Department of Micro Engineering, Graduate School of Engineering, Kyoto University, Kyoto Daigaku-katsura, Nishikyo-ku, Kyoto, 615-8530, Japan; Institute for Frontier Life and Medical Sciences, Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan; Division of Systemic Life Science, Graduate School of Biostudies, Kyoto University, Yoshida-Konoecho, Sakyo-ku, Kyoto, 606-8501, Japan.
| | - Taiji Adachi
- Department of Micro Engineering, Graduate School of Engineering, Kyoto University, Kyoto Daigaku-katsura, Nishikyo-ku, Kyoto, 615-8530, Japan; Institute for Frontier Life and Medical Sciences, Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan; Division of Systemic Life Science, Graduate School of Biostudies, Kyoto University, Yoshida-Konoecho, Sakyo-ku, Kyoto, 606-8501, Japan
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Transplantation of Fibroblast Sheets with Blood Mononuclear Cell Culture Exerts Cardioprotective Effects by Enhancing Anti-Inflammation and Vasculogenic Potential in Rat Experimental Autoimmune Myocarditis Model. BIOLOGY 2022; 11:biology11010106. [PMID: 35053105 PMCID: PMC8772944 DOI: 10.3390/biology11010106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Revised: 12/26/2021] [Accepted: 12/30/2021] [Indexed: 11/28/2022]
Abstract
Simple Summary Fulminant myocarditis (FM) is a serious inflammatory lesion of the myocardium accompanied by cardiac dysfunction, transitioning to end-stage heart failure. Due to such a difficult pathology, a therapeutic strategy that exerts a steadfast effect has yet to be developed. Blood mononuclear cells (MNCs) have been previously shown to enhance the quality and quantity of cellular fractions (QQMNCs) with anti-inflammatory and vasculogenic potential using the one culture system. The aim of this study was to investigate whether transplantation therapy with hybrid cell sheets of fibroblasts and QQMNCs improves cardiac function in a rat model with experimental autoimmune myocarditis (EAM) induced by purified porcine cardiac myosin. The transplanted hybrid cell sheet exerts cardioprotective effects against EAM, resulting in limited left ventricular remodeling and partially improved cardiac functions due to revascularization, anti-inflammation, and anti-fibrosis. Thus, tissue engineering using hybrid cell sheets of fibroblasts constructed with QQMNCs is expected to provide an effective therapeutic option for patients with severe FM. Abstract Fulminant myocarditis causes impaired cardiac function, leading to poor prognosis and heart failure. Cell sheet engineering is an effective therapeutic option for improving cardiac function. Naïve blood mononuclear cells (MNCs) have been previously shown to enhance the quality and quantity of cellular fractions (QQMNCs) with anti-inflammatory and vasculogenic potential using the one culture system. Herein, we investigated whether autologous cell sheet transplant with QQMNCs improves cardiac function in a rat model with experimental autoimmune myocarditis (EAM). Fibroblast sheets (F-sheet), prepared from EAM rats, were co-cultured with or without QQMNCs (QQ+F sheet) on temperature-responsive dishes. QQ+F sheet induced higher expression of anti-inflammatory and vasculogenic genes (Vegf-b, Hgf, Il-10, and Mrc1/Cd206) than the F sheet. EAM rats were transplanted with either QQ+F sheet or F-sheet, and the left ventricular (LV) hemodynamic analysis was performed using cardiac catheterization. Among the three groups (QQ+F sheet, F-sheet, operation control), the QQ+F sheet transplant group showed alleviation of end-diastolic pressure–volume relationship on a volume load to the same level as that in the healthy group. Histological analysis revealed that QQ+F sheet transplantation promoted revascularization and mitigated fibrosis by limiting LV remodeling. Therefore, autologous QQMNC-modified F-sheets may be a beneficial therapeutic option for EAM.
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