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Wang JJ, Zheng Y, Li YL, Xiao Y, Ren YY, Tian YQ. Emerging role of mesenchymal stem cell-derived exosomes in the repair of acute kidney injury. World J Stem Cells 2025; 17:103360. [DOI: 10.4252/wjsc.v17.i3.103360] [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: 11/16/2024] [Revised: 12/26/2024] [Accepted: 02/13/2025] [Indexed: 03/21/2025] Open
Abstract
Acute kidney injury (AKI) is a clinical syndrome characterized by a rapid deterioration in kidney function and has a significant impact on patient health and survival. Mesenchymal stem cells (MSCs) have the potential to enhance renal function by suppressing the expression of cell cycle inhibitors and reducing the expression of senescence markers and microRNAs via paracrine and endocrine mechanisms. MSC-derived exosomes can alleviate AKI symptoms by regulating DNA damage, apoptosis, and other related signaling pathways through the delivery of proteins, microRNAs, long-chain noncoding RNAs, and circular RNAs. This technique is both safe and effective. MSC-derived exosomes may have great application prospects in the treatment of AKI. Understanding the underlying mechanisms will foster the development of new and promising therapeutic strategies against AKI. This review focused on recent advancements in the role of MSCs in AKI repair as well as the mechanisms underlying the role of MSCs and their secreted exosomes. It is anticipated that novel and profound insights into the functionality of MSCs and their derived exosomes will emerge.
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Affiliation(s)
- Juan-Juan Wang
- Clinical Laboratory, The First People’s Hospital of Yancheng, Yancheng First Hospital, Affiliated Hospital of Nanjing University Medical School, Yancheng 224000, Jiangsu Province, China
| | - Yu Zheng
- Clinical Laboratory, The First People’s Hospital of Yancheng, Yancheng First Hospital, Affiliated Hospital of Nanjing University Medical School, Yancheng 224000, Jiangsu Province, China
| | - Yan-Lin Li
- Clinical Laboratory, The First People’s Hospital of Yancheng, Yancheng First Hospital, Affiliated Hospital of Nanjing University Medical School, Yancheng 224000, Jiangsu Province, China
| | - Yin Xiao
- Department of Medical Imaging, The Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China
| | - Yang-Yang Ren
- Clinical Laboratory, Xinyi People’s Hospital, Xuzhou 221000, Jiangsu Province, China
| | - Yi-Qing Tian
- Clinical Laboratory, Xuzhou Central Hospital, Xuzhou 221000, Jiangsu Province, China
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Renu K. Exosomes derived from human adipose mesenchymal stem cells act as a therapeutic target for oral submucous fibrosis. JOURNAL OF STOMATOLOGY, ORAL AND MAXILLOFACIAL SURGERY 2025:102224. [PMID: 39765310 DOI: 10.1016/j.jormas.2025.102224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/03/2024] [Accepted: 01/03/2025] [Indexed: 01/11/2025]
Abstract
Oral submucosal fibrosis is a highly malignant oral condition that necessitates the use of sophisticated therapeutic procedures. OSF is a multifactorial precancerous condition induced by areca nut chewing, deficiencies in vitamins and trace minerals, immunological aspects, and hereditary factors. Adipose tissue-derived mesenchymal stem cells possess the capability for multidirectional activation and are extensively distributed throughout the body. They have minimal immunogenicity and are extensively utilized in cancer treatment. Exosomes are extracellular vesicles produced by the intracellular route. They are biological carriers comprising microRNA, messenger RNA, lipids and proteins crucial for intercellular communication. ADSC exosomes, serving as a vehicle for miRNA, possess accessibility and little immunogenicity. They can significantly contribute to adipose tissue regrowth, angiogenesis, immunological modulation, and tissue repair. ADSC-Exo exhibits antifibrotic properties and may serve as a potential treatment for OSF. This review presents a novel therapeutic approach and clarifies the precise mechanisms involved in the clinical management of OSF using ADSC-Exo.
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Affiliation(s)
- Kaviyarasi Renu
- Centre of Molecular Medicine and Diagnostics (COMManD), Department of Biochemistry, Saveetha Dental College & Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai - 600077, Tamil Nadu, India.
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Moñivas Gallego E, Zurita Castillo M. Mesenchymal stem cell therapy in ischemic stroke trials. A systematic review. Regen Ther 2024; 27:301-306. [PMID: 38633415 PMCID: PMC11021793 DOI: 10.1016/j.reth.2024.03.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2024] [Revised: 03/11/2024] [Accepted: 03/24/2024] [Indexed: 04/19/2024] Open
Abstract
Cerebrovascular accidents, also known as strokes, are the leading cause of permanent disability in society, presenting significant socioeconomic and healthcare costs. They can be caused by ischemic factors or hemorrhages, with ischemic strokes being the most common among the population. Therapies for patients suffering from this condition are limited and primarily focus on acute-phase treatment. In recent years, there has been an increase in cellular therapies, employing Stem Cells to mitigate or eliminate the consequences arising from this disease. Mesenchymal Stem Cells (MSCs) hold substantial therapeutic potential in Nervous System pathologies due to their low antigenicity and capacity to differentiate into various human tissues, such as adipogenic, chondrogenic, and osteogenic tissues. This study conducts a literature review using the "clinical trials" and "Pubmed" database, summarizing all ongoing clinical trials for ischemic strokes that utilize MSCs as treatment.
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Affiliation(s)
- Ester Moñivas Gallego
- Fundación para la Investigación Biomédica del Hospital Universitario Puerta de Hierro Majadahonda, Spain
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Mu Y, Zhang X, Zhang L, Luo R, Zhang Y, Wang M. MSC Exosomes Containing Valproic Acid Promote Wound Healing by Modulating Inflammation and Angiogenesis. Molecules 2024; 29:4281. [PMID: 39275128 PMCID: PMC11397650 DOI: 10.3390/molecules29174281] [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: 08/06/2024] [Revised: 08/31/2024] [Accepted: 09/05/2024] [Indexed: 09/16/2024] Open
Abstract
PURPOSE Chronic wounds that are difficult to heal pose a major challenge for clinicians and researchers. Currently, common treatment methods focus on isolating the wound from the outside world, relying on the tissue at the wound site to grow and heal unaided. Umbilical cord mesenchymal stem cell (MSC) exosomes can promote wound healing by enhancing new blood vessel growth at the wound site. Valproic acid (VPA) reduces the inflammatory response and acts on macrophages to accelerate wound closure. In this study, VPA was loaded into umbilical cord MSC exosomes to form a drug carrier exosome (VPA-EXO) with the aim of investigating the effect of VPA-EXO on wound healing. METHODS This study first isolated and obtained umbilical cord MSC exosomes, then added VPA to the exosomes and explored the ability of VPA-EXO to promote the proliferation and migration of human skin fibroblasts (HSFs) and human umbilical vein endothelial cells (HUVECs), as well as the ability to promote the angiogenesis of HUVECs, by using scratch, Transwell, and angiogenesis assays. An in vitro cell model was established and treated with VPA-EXO, and the expression levels of inflammation and pro-angiogenesis-related proteins and genes were examined using Western blot and qRT-PCR. The therapeutic effect of VPA-EXO on promoting wound healing in a whole skin wound model was investigated using image analysis of the wound site, H&E staining, and immunohistochemical staining experiments in a mouse wound model. RESULTS The in vitro model showed that VPA-EXO effectively promoted the proliferation and migration of human skin fibroblast cells and human umbilical vein endothelial cells; significantly inhibited the expression of MMP-9, IL-1β, IL-8, TNF-α, and PG-E2; and promoted the expression of vascular endothelial growth factors. In the mouse wound model, VPA-EXO reduced inflammation at the wound site, accelerated wound healing, and significantly increased the collagen content of tissue at the wound site. CONCLUSIONS As a complex with dual efficacy in simultaneously promoting tissue regeneration and inhibiting inflammation, VPA-EXO has potential applications in tissue wound healing and vascular regeneration. In future studies, we will further investigate the mechanism of action and application scenarios of drug-loaded exosome complexes in different types of wound healing and vascular regeneration.
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Affiliation(s)
- Yujie Mu
- School of Light Industry Science and Engineering, Beijing Technology and Business University, Beijing 100048, China
| | - Xiaona Zhang
- School of Light Industry Science and Engineering, Beijing Technology and Business University, Beijing 100048, China
| | - Linfeng Zhang
- School of Light Industry Science and Engineering, Beijing Technology and Business University, Beijing 100048, China
| | - Ruting Luo
- School of Light Industry Science and Engineering, Beijing Technology and Business University, Beijing 100048, China
| | - Yin Zhang
- School of Light Industry Science and Engineering, Beijing Technology and Business University, Beijing 100048, China
| | - Min Wang
- School of Light Industry Science and Engineering, Beijing Technology and Business University, Beijing 100048, China
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Wang L, Li T, Ma X, Li Y, Li Z, Li Z, Yu N, Huang J, Han Q, Long X. Exosomes from human adipose-derived mesenchymal stem cells attenuate localized scleroderma fibrosis by the let-7a-5p/TGF-βR1/Smad axis. J Dermatol Sci 2023; 112:31-38. [PMID: 37743142 DOI: 10.1016/j.jdermsci.2023.09.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Revised: 07/21/2023] [Accepted: 09/05/2023] [Indexed: 09/26/2023]
Abstract
BACKGROUND Inflammation and fibrosis of the skin are characteristics of localized scleroderma (LS). Emerging evidence has demonstrated that exosomes from human adipose tissue-derived mesenchymal stem cells (ADSC-Exo) could alleviate skin fibrosis. OBJECTIVE The impact and potential mechanism of ADSC-Exo on LS fibrosis was examined. METHODS ADSC-Exo was isolated and identified. The effects of ADSC-Exo on the abilities of proliferation and migration of LS-derived fibroblasts (LSFs) were assessed by CCK-8 and scratch assays, respectively. qRT-PCR, western blot, and immunofluorescence were conducted to detect LSFs stimulated with ADSC-Exo, ADSC-ExoAnti-let-7a-5p, let-7a-5p mimic/TGF-βR1 shRNA virus, and negative controls. The impact of ADSC-Exo on C57BL/6j LS mice was evaluated by photographic morphology, hematoxylin-eosin (H&E), Masson's trichrome, and immunohistochemical staining. RESULTS The verified ADSC-Exo limited the proliferation and migration of LSFs and reduced the expression of COL1, COL3, α-SMA, TGF-βR1, and p-Smad2/ 3 in vitro and in vivo. TGF-βR1 knockdown and let-7a-5p mimic in LSFs reduced the expression of COL1, COL3, α-SMA, and p-Smad2/3. However, compared with the ADSC-ExoNC group, the dermal thickness was increased, collagen arrangement was disordered, and α-SMA and TGF-βR1 levels were increased after exposure to ADSC-ExoAnti-let-7a-5p. CONCLUSIONS In this study, it might show that ADSC-Exo may successfully prevent LSF bioactivity, collagen deposition, and myofibroblast trans-differentiation. Additionally, we confirmed that let-7a-5p in ADSC-Exo could directly target TGF-R1 to control the Smad pathway and reduce fibrosis in LSFs. Our work offered a brand-new therapeutic approach and clarified the unique mechanism for the clinical management of LS.
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Affiliation(s)
- Liquan Wang
- Department of Plastic and Aesthetic Surgery, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China
| | - Tianhao Li
- Department of Plastic and Aesthetic Surgery, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China
| | - Xuda Ma
- Department of Plastic and Aesthetic Surgery, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China
| | - Yunzhu Li
- Department of Plastic and Aesthetic Surgery, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China
| | - Zhujun Li
- Department of Plastic and Aesthetic Surgery, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China
| | - Ziming Li
- Department of Plastic and Aesthetic Surgery, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China
| | - Nanze Yu
- Department of Plastic and Aesthetic Surgery, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China
| | - Jiuzuo Huang
- Department of Plastic and Aesthetic Surgery, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China
| | - Qin Han
- Beijing Key Laboratory (No.BZO381), Center of Excellence in Tissue Engineering Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, Beijing, China.
| | - Xiao Long
- Department of Plastic and Aesthetic Surgery, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China.
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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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Bálint L, Nelson-Maney N, Tian Y, Serafin DS, Caron KM. Clinical Potential of Adrenomedullin Signaling in the Cardiovascular System. Circ Res 2023; 132:1185-1202. [PMID: 37104556 PMCID: PMC10155262 DOI: 10.1161/circresaha.123.321673] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Accepted: 03/16/2023] [Indexed: 04/29/2023]
Abstract
Numerous clinical studies have revealed the utility of circulating AM (adrenomedullin) or MR-proAM (mid-regional proAM 45-92) as an effective prognostic and diagnostic biomarker for a variety of cardiovascular-related pathophysiologies. Thus, there is strong supporting evidence encouraging the exploration of the AM-CLR (calcitonin receptor-like receptor) signaling pathway as a therapeutic target. This is further bolstered because several drugs targeting the shared CGRP (calcitonin gene-related peptide)-CLR pathway are already Food and Drug Administration-approved and on the market for the treatment of migraine. In this review, we summarize the AM-CLR signaling pathway and its modulatory mechanisms and provide an overview of the current understanding of the physiological and pathological roles of AM-CLR signaling and the yet untapped potentials of AM as a biomarker or therapeutic target in cardiac and vascular diseases and provide an outlook on the recently emerged strategies that may provide further boost to the possible clinical applications of AM signaling.
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Affiliation(s)
- László Bálint
- Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill; 111 Mason Farm Road, Chapel Hill, North Carolina, USA 27599
| | - Nathan Nelson-Maney
- Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill; 111 Mason Farm Road, Chapel Hill, North Carolina, USA 27599
| | - Yanna Tian
- Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill; 111 Mason Farm Road, Chapel Hill, North Carolina, USA 27599
| | - D. Stephen Serafin
- Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill; 111 Mason Farm Road, Chapel Hill, North Carolina, USA 27599
| | - Kathleen M. Caron
- Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill; 111 Mason Farm Road, Chapel Hill, North Carolina, USA 27599
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Mechanotransduction of mesenchymal stem cells (MSCs) during cardiomyocytes differentiation. Heliyon 2022; 8:e11624. [DOI: 10.1016/j.heliyon.2022.e11624] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Revised: 09/15/2022] [Accepted: 11/09/2022] [Indexed: 11/16/2022] Open
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Luo Y, Xu X, Ye Z, Xu Q, Li J, Liu N, Du Y. 3D bioprinted mesenchymal stromal cells in skin wound repair. Front Surg 2022; 9:988843. [PMID: 36311952 PMCID: PMC9614372 DOI: 10.3389/fsurg.2022.988843] [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: 07/07/2022] [Accepted: 09/20/2022] [Indexed: 11/07/2022] Open
Abstract
Skin tissue regeneration and repair is a complex process involving multiple cell types, and current therapies are limited to promoting skin wound healing. Mesenchymal stromal cells (MSCs) have been proven to enhance skin tissue repair through their multidifferentiation and paracrine effects. However, there are still difficulties, such as the limited proliferative potential and the biological processes that need to be strengthened for MSCs in wound healing. Recently, three-dimensional (3D) bioprinting has been applied as a promising technology for tissue regeneration. 3D-bioprinted MSCs could maintain a better cell ability for proliferation and expression of biological factors to promote skin wound healing. It has been reported that 3D-bioprinted MSCs could enhance skin tissue repair through anti-inflammatory, cell proliferation and migration, angiogenesis, and extracellular matrix remodeling. In this review, we will discuss the progress on the effect of MSCs and 3D bioprinting on the treatment of skin tissue regeneration, as well as the perspective and limitations of current research.
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Csöbönyeiová M, Beerová N, Klein M, Debreová-Čeháková M, Danišovič Ľ. Cell-Based and Selected Cell-Free Therapies for Myocardial Infarction: How Do They Compare to the Current Treatment Options? Int J Mol Sci 2022; 23:10314. [PMID: 36142245 PMCID: PMC9499607 DOI: 10.3390/ijms231810314] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Revised: 09/03/2022] [Accepted: 09/05/2022] [Indexed: 11/17/2022] Open
Abstract
Because of cardiomyocyte death or dysfunction frequently caused by myocardial infarction (MI), heart failure is a leading cause of morbidity and mortality in modern society. Paradoxically, only limited and non-curative therapies for heart failure or MI are currently available. As a result, over the past two decades research has focused on developing cell-based approaches promoting the regeneration of infarcted tissue. Cell-based therapies for myocardial regeneration include powerful candidates, such as multipotent stem cells (mesenchymal stem cells (MSCs), bone-marrow-derived stem cells, endothelial progenitor cells, and hematopoietic stem cells) and induced pluripotent stem cells (iPSCs). These possess unique properties, such as potency to differentiate into desired cell types, proliferation capacity, and patient specificity. Preclinical and clinical studies have demonstrated modest improvement in the myocardial regeneration and reduced infarcted areas upon transplantation of pluripotent or multipotent stem cells. Another cell population that need to be considered as a potential source for cardiac regeneration are telocytes found in different organs, including the heart. Their therapeutic effect has been studied in various heart pathologies, such as MI, arrhythmias, or atrial amyloidosis. The most recent cell-free therapeutic tool relies on the cardioprotective effect of complex cargo carried by small membrane-bound vesicles-exosomes-released from stem cells via exocytosis. The MSC/iPSC-derived exosomes could be considered a novel exosome-based therapy for cardiovascular diseases thanks to their unique content. There are also other cell-free approaches, e.g., gene therapy, or acellular cardiac patches. Therefore, our review provides the most recent insights into the novel strategies for myocardial repair based on the regenerative potential of different cell types and cell-free approaches.
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Affiliation(s)
- Mária Csöbönyeiová
- National Institute of Rheumatic Diseases, Nábrežie I. Krasku 4, 921 12 Piešťany, Slovakia
- Institute of Histology and Embryology, Faculty of Medicine, Comenius University, Sasinkova 4, 811 08 Bratislava, Slovakia
| | - Nikoleta Beerová
- Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University, Sasinkova 4, 811 08 Bratislava, Slovakia
| | - Martin Klein
- National Institute of Rheumatic Diseases, Nábrežie I. Krasku 4, 921 12 Piešťany, Slovakia
- Institute of Histology and Embryology, Faculty of Medicine, Comenius University, Sasinkova 4, 811 08 Bratislava, Slovakia
| | - Michaela Debreová-Čeháková
- National Institute of Rheumatic Diseases, Nábrežie I. Krasku 4, 921 12 Piešťany, Slovakia
- Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University, Sasinkova 4, 811 08 Bratislava, Slovakia
| | - Ľuboš Danišovič
- National Institute of Rheumatic Diseases, Nábrežie I. Krasku 4, 921 12 Piešťany, Slovakia
- Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University, Sasinkova 4, 811 08 Bratislava, Slovakia
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Ahmed L, Al-Massri K. New Approaches for Enhancement of the Efficacy of Mesenchymal Stem Cell-Derived Exosomes in Cardiovascular Diseases. Tissue Eng Regen Med 2022; 19:1129-1146. [PMID: 35867309 DOI: 10.1007/s13770-022-00469-x] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Revised: 06/03/2022] [Accepted: 06/08/2022] [Indexed: 11/28/2022] Open
Abstract
Cardiovascular diseases (CVDs) remain a major health concern worldwide, where mesenchymal stem cells (MSCs) therapy gives great promise in their management through their regenerative and paracrine actions. In recent years, many studies have shifted from the use of transplanted stem cells to their secreted exosomes for the management of various CVDs and cardiovascular-related diseases including atherosclerosis, stroke, myocardial infarction, heart failure, peripheral arterial diseases, and pulmonary hypertension. In different models, MSC-derived exosomes have shown beneficial outcomes similar to cell therapy concerning regenerative and neovascular actions in addition to their anti-apoptotic, anti-remodeling, and anti-inflammatory actions. Compared with their parent cells, exosomes have also demonstrated several advantages, including lower immunogenicity and no risk of tumor formation. However, the maintenance of stability and efficacy of exosomes after in vivo transplantation is still a major concern in their clinical application. Recently, new approaches have been developed to enhance their efficacy and stability including their preconditioning before transplantation, use of genetically modified MSC-derived exosomes, or their utilization as a targeted drug delivery system. Herein, we summarized the use of MSC-derived exosomes as therapies in different CVDs in addition to recent advances for the enhancement of their efficacy in these conditions.
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Affiliation(s)
- Lamiaa Ahmed
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Kasr El Aini St., Cairo, 11562, Egypt.
| | - Khaled Al-Massri
- Department of Pharmacy and Biotechnology, Faculty of Medicine and Health Sciences, University of Palestine, Gaza, Palestine
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12
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Liu Y, Chen J, Liang H, Cai Y, Li X, Yan L, Zhou L, Shan L, Wang H. Human umbilical cord-derived mesenchymal stem cells not only ameliorate blood glucose but also protect vascular endothelium from diabetic damage through a paracrine mechanism mediated by MAPK/ERK signaling. Stem Cell Res Ther 2022; 13:258. [PMID: 35715841 PMCID: PMC9205155 DOI: 10.1186/s13287-022-02927-8] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Accepted: 03/22/2022] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Endothelial damage is an initial step of macro- and micro-vasculature dysfunctions in diabetic patients, accounting for a high incidence of diabetic vascular complications, such as atherosclerosis, nephropathy, retinopathy, and neuropathy. However, clinic lacks effective therapeutics targeting diabetic vascular complications. In field of regenerative medicine, mesenchymal stem cells, such as human umbilical cord-derived MSCs (hucMSCs), have great potential in treating tissue damage. METHODS To determine whether hucMSCs infusion could repair diabetic vascular endothelial damage and how it works, this study conducted in vivo experiment on streptozotocin-induced diabetic rat model to test body weight, fasting blood glucose (FBG), serum ICAM-1 and VCAM-1 levels, histopathology and immunohistochemical staining of aorta segments. In vitro experiment was further conducted to determine the effects of hucMSCs on diabetic vascular endothelial damage, applying assays of resazurin staining, MTT cell viability, wound healing, transwell migration, and matrigel tube formation on human umbilical vein endothelial cells (HUVECs). RNA sequencing (RNAseq) and molecular experiment were conducted to clarify the mechanism of hucMSCs. RESULTS The in vivo data revealed that hucMSCs partially restore the alterations of body weight, FBG, serum ICAM-1 and VCAM-1 levels, histopathology of aorta and reversed the abnormal phosphorylation of ERK in diabetic rats. By using the conditioned medium of hucMSCs (MSC-CM), the in vitro data revealed that hucMSCs improved cell viability, wound healing, migration and angiogenesis of the high glucose-damaged HUVECs through a paracrine action mode, and the altered gene expressions of IL-6, TNF-α, ICAM-1, VCAM-1, BAX, P16, P53 and ET-1 were significantly restored by MSC-CM. RNAseq incorporated with real-time PCR and Western blot results clarified that high glucose activated MAPK/ERK signaling in HUVECs, while MSC-CM reversed the abnormal phosphorylation of ERK and overexpressions of MKNK2, ERBB3, MYC and DUSP5 in MAPK/ERK signaling pathway. CONCLUSIONS HucMSCs not only ameliorated blood glucose but also protected vascular endothelium from diabetic damage, in which MAPK/ERK signaling mediated its molecular mechanism of paracrine action. Our findings provided novel knowledge of hucMSCs in the treatment of diabetes and suggested a prospective strategy for the clinical treatment of diabetic vascular complications.
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Affiliation(s)
- Yi Liu
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Jingan Chen
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Haowei Liang
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Yueqin Cai
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Xinyue Li
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Li Yan
- The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China.,Cell Resource Bank and Integrated Cell Preparation Center of Xiaoshan District, Hangzhou Regional Cell Preparation Center (Shangyu Biotechnology Co., Ltd), Hangzhou, China
| | - Li Zhou
- The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China
| | - Letian Shan
- The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China. .,Cell Resource Bank and Integrated Cell Preparation Center of Xiaoshan District, Hangzhou Regional Cell Preparation Center (Shangyu Biotechnology Co., Ltd), Hangzhou, China.
| | - Hui Wang
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
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Xu JH, Xu SQ, Ding SL, Yang H, Huang X, Shi HF. Bone marrow mesenchymal stem cells alleviate the formation of pathological scars in rats. Regen Ther 2022; 20:86-94. [PMID: 35509267 PMCID: PMC9048073 DOI: 10.1016/j.reth.2022.03.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2021] [Revised: 01/30/2022] [Accepted: 03/08/2022] [Indexed: 11/26/2022] Open
Abstract
Introduction Methods Results Conclusions
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Razavi Tousi SMT, Sharifi M, Naseroleslami M, Azizi Y, Aboutaleb N. Mesenchymal Stem Cells Derived from Human Amniotic Membrane Increase VEGF and Extenuate Fibrosis in Heart Failure Rats. IRANIAN JOURNAL OF SCIENCE AND TECHNOLOGY, TRANSACTIONS A: SCIENCE 2022; 46:781-791. [DOI: 10.1007/s40995-022-01307-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/03/2021] [Accepted: 05/02/2022] [Indexed: 01/03/2025]
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15
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Sharma A, Gupta S, Archana S, Verma RS. Emerging Trends in Mesenchymal Stem Cells Applications for Cardiac Regenerative Therapy: Current Status and Advances. Stem Cell Rev Rep 2022; 18:1546-1602. [PMID: 35122226 DOI: 10.1007/s12015-021-10314-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/29/2021] [Indexed: 12/29/2022]
Abstract
Irreversible myocardium infarction is one of the leading causes of cardiovascular disease (CVD) related death and its quantum is expected to grow in coming years. Pharmacological intervention has been at the forefront to ameliorate injury-related morbidity and mortality. However, its outcomes are highly skewed. As an alternative, stem cell-based tissue engineering/regenerative medicine has been explored quite extensively to regenerate the damaged myocardium. The therapeutic modality that has been most widely studied both preclinically and clinically is based on adult multipotent mesenchymal stem cells (MSC) delivered to the injured heart. However, there is debate over the mechanistic therapeutic role of MSC in generating functional beating cardiomyocytes. This review intends to emphasize the role and use of MSC in cardiac regenerative therapy (CRT). We have elucidated in detail, the various aspects related to the history and progress of MSC use in cardiac tissue engineering and its multiple strategies to drive cardiomyogenesis. We have further discussed with a focus on the various therapeutic mechanism uncovered in recent times that has a significant role in ameliorating heart-related problems. We reviewed recent and advanced technologies using MSC to develop/create tissue construct for use in cardiac regenerative therapy. Finally, we have provided the latest update on the usage of MSC in clinical trials and discussed the outcome of such studies in realizing the full potential of MSC use in clinical management of cardiac injury as a cellular therapy module.
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Affiliation(s)
- Akriti Sharma
- Stem Cell and Molecular Biology Laboratory, Bhupat and Jyoti Mehta School of Biosciences, Department of Biotechnology, Indian Institute of Technology-Madras, Chennai, 600036, Tamil Nadu, India
| | - Santosh Gupta
- Stem Cell and Molecular Biology Laboratory, Bhupat and Jyoti Mehta School of Biosciences, Department of Biotechnology, Indian Institute of Technology-Madras, Chennai, 600036, Tamil Nadu, India
| | - S Archana
- Stem Cell and Molecular Biology Laboratory, Bhupat and Jyoti Mehta School of Biosciences, Department of Biotechnology, Indian Institute of Technology-Madras, Chennai, 600036, Tamil Nadu, India
| | - Rama Shanker Verma
- Stem Cell and Molecular Biology Laboratory, Bhupat and Jyoti Mehta School of Biosciences, Department of Biotechnology, Indian Institute of Technology-Madras, Chennai, 600036, Tamil Nadu, India.
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Piryani AK, Kilari S, Takahashi E, DeMartino RR, Mandrekar J, Dietz AB, Misra S. Rationale and Trial Design of MesEnchymal Stem Cell Trial in Preventing Venous Stenosis of Hemodialysis Vascular Access Arteriovenous Fistula (MEST AVF Trial). KIDNEY360 2021; 2:1945-1952. [PMID: 35419530 PMCID: PMC8986037 DOI: 10.34067/kid.0005182021] [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: 08/10/2021] [Accepted: 09/10/2021] [Indexed: 02/04/2023]
Abstract
Background Hemodialysis arteriovenous fistulas (AVFs) are the preferred vascular access for patients on hemodialysis. In the Hemodialysis Fistula Maturation Study, 44% of the patients achieved unassisted maturation of their fistula without needing an intervention. Venous neointimal hyperplasia (VNH) and subsequent venous stenosis are responsible for lack of maturation. There are no therapies that can prevent VNH/VS formation. The goal of this paper is to present the background, rationale, and trial design of an innovative phase 1/2 clinical study that is investigating the safety of autologous adipose-derived mesenchymal stem cells delivered locally to the adventitia of newly created upper extremity radiocephalic (RCF) or brachiocephalic fistula (BCF). Methods The rationale and preclinical studies used to obtain a physician-sponsored investigational new drug trial are discussed. The trial design and end points are discussed. Results This is an ongoing trial that will complete this year. Conclusion This is a phase 1/2 single-center, randomized trial that will investigate the safety and efficacy of autologous AMSCs in promoting maturation in new upper-extremity AVFs.Clinical Trial registration number: NCT02808208.
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Affiliation(s)
| | | | | | | | - Jay Mandrekar
- Department of Biostatistics, Mayo Clinic, Rochester, Minnesota
| | - Allan B. Dietz
- Division of Transfusion Medicine and Laboratory Medicine, Mayo Clinic, Rochester, Minnesota
| | - Sanjay Misra
- Department of Radiology, Mayo Clinic, Rochester, Minnesota
- Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota
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Hopes and Hurdles of Employing Mesenchymal Stromal Cells in the Treatment of Cardiac Fibrosis. Int J Mol Sci 2021; 22:ijms222313000. [PMID: 34884805 PMCID: PMC8657815 DOI: 10.3390/ijms222313000] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 11/25/2021] [Accepted: 11/29/2021] [Indexed: 12/04/2022] Open
Abstract
Excessive cardiac fibrosis plays a crucial role in almost all types of heart disease. Generally, cardiac fibrosis is a scarring process triggered in response to stress, injury, or aging and is characterized by the accumulation of activated myofibroblasts that deposit high levels of extracellular matrix proteins in the myocardium. While it is beneficial for cardiac repair in the short term, it can also result in pathological remodeling, tissue stiffening, and cardiac dysfunction, contributing to the progression of heart failure, arrhythmia, and sudden cardiac death. Despite its high prevalence, there is a lack of effective and safe therapies that specifically target myofibroblasts to inhibit or even reverse pathological cardiac fibrosis. In the past few decades, cell therapy has been under continuous evaluation as a potential treatment strategy, and several studies have shown that transplantation of mesenchymal stromal cells (MSCs) can reduce cardiac fibrosis and improve heart function. Mechanistically, it is believed that the heart benefits from MSC therapy by stimulating innate anti-fibrotic and regenerative reactions. The mechanisms of action include paracrine signaling and cell-to-cell interactions. In this review, we provide an overview of the anti-fibrotic properties of MSCs and approaches to enhance them and discuss future directions of MSCs for the treatment of cardiac fibrosis.
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Functions of Mesenchymal Stem Cells in Cardiac Repair. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1312:39-50. [PMID: 33330961 DOI: 10.1007/5584_2020_598] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Myocardial infarction (MI) and heart failure (HF) are significant contributors of mortality worldwide. Mesenchymal stem cells (MSCs) hold a great potential for cardiac regenerative medicine-based therapies. Their therapeutic potential has been widely investigated in various in-vitro and in-vivo preclinical models. Besides, they have been tested in clinical trials of MI and HF with various outcomes. Differentiation to lineages of cardiac cells, neovascularization, anti-fibrotic, anti-inflammatory, anti-apoptotic and immune modulatory effects are the main drivers of MSC functions during cardiac repair. However, the main mechanisms regulating these functions and cross-talk between cells are not fully known yet. Increasing line of evidence also suggests that secretomes of MSCs and/or their extracellular vesicles play significant roles in a paracrine manner while mediating these functions. This chapter aims to summarize and highlight cardiac repair functions of MSCs during cardiac repair.
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19
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The Role of MSC in Wound Healing, Scarring and Regeneration. Cells 2021; 10:cells10071729. [PMID: 34359898 PMCID: PMC8305394 DOI: 10.3390/cells10071729] [Citation(s) in RCA: 198] [Impact Index Per Article: 49.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Revised: 07/02/2021] [Accepted: 07/03/2021] [Indexed: 02/06/2023] Open
Abstract
Tissue repair and regeneration after damage is not completely understood, and current therapies to support this process are limited. The wound healing process is associated with cell migration and proliferation, extracellular matrix remodeling, angiogenesis and re-epithelialization. In normal conditions, a wound will lead to healing, resulting in reparation of the tissue. Several risk factors, chronic inflammation, and some diseases lead to a deficient wound closure, producing a scar that can finish with a pathological fibrosis. Mesenchymal stem/stromal cells (MSCs) are widely used for their regenerative capacity and their possible therapeutically potential. Derived products of MSCs, such as exosomes or extravesicles, have shown a therapeutic potential similar to MSCs, and these cell-free products may be interesting in clinics. MSCs or their derivative products have shown paracrine beneficial effects, regulating inflammation, modifying the fibroblast activation and production of collagen and promoting neovascularization and re-epithelialization. This review describes the effects of MSCs and their derived products in each step of the wound repair process. As well, it reviews the pre-clinical and clinical use of MSCs to benefit in skin wound healing in diabetic associated wounds and in pathophysiological fibrosis.
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20
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Sandonà M, Di Pietro L, Esposito F, Ventura A, Silini AR, Parolini O, Saccone V. Mesenchymal Stromal Cells and Their Secretome: New Therapeutic Perspectives for Skeletal Muscle Regeneration. Front Bioeng Biotechnol 2021; 9:652970. [PMID: 34095095 PMCID: PMC8172230 DOI: 10.3389/fbioe.2021.652970] [Citation(s) in RCA: 55] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Accepted: 04/01/2021] [Indexed: 12/14/2022] Open
Abstract
Mesenchymal stromal cells (MSCs) are multipotent cells found in different tissues: bone marrow, peripheral blood, adipose tissues, skeletal muscle, perinatal tissues, and dental pulp. MSCs are able to self-renew and to differentiate into multiple lineages, and they have been extensively used for cell therapy mostly owing to their anti-fibrotic and immunoregulatory properties that have been suggested to be at the basis for their regenerative capability. MSCs exert their effects by releasing a variety of biologically active molecules such as growth factors, chemokines, and cytokines, either as soluble proteins or enclosed in extracellular vesicles (EVs). Analyses of MSC-derived secretome and in particular studies on EVs are attracting great attention from a medical point of view due to their ability to mimic all the therapeutic effects produced by the MSCs (i.e., endogenous tissue repair and regulation of the immune system). MSC-EVs could be advantageous compared with the parental cells because of their specific cargo containing mRNAs, miRNAs, and proteins that can be biologically transferred to recipient cells. MSC-EV storage, transfer, and production are easier; and their administration is also safer than MSC therapy. The skeletal muscle is a very adaptive tissue, but its regenerative potential is altered during acute and chronic conditions. Recent works demonstrate that both MSCs and their secretome are able to help myofiber regeneration enhancing myogenesis and, interestingly, can be manipulated as a novel strategy for therapeutic interventions in muscular diseases like muscular dystrophies or atrophy. In particular, MSC-EVs represent promising candidates for cell free-based muscle regeneration. In this review, we aim to give a complete picture of the therapeutic properties and advantages of MSCs and their products (MSC-derived EVs and secreted factors) relevant for skeletal muscle regeneration in main muscular diseases.
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Affiliation(s)
- Martina Sandonà
- Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Fondazione Santa Lucia, Rome, Italy
| | - Lorena Di Pietro
- Dipartimento di Scienze della Vita e Sanità Pubblica, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Federica Esposito
- Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Fondazione Santa Lucia, Rome, Italy
| | - Alessia Ventura
- Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Fondazione Santa Lucia, Rome, Italy
| | - Antonietta Rosa Silini
- Centro di Ricerca "E. Menni", Fondazione Poliambulanza - Istituto Ospedaliero, Brescia, Italy
| | - Ornella Parolini
- Dipartimento di Scienze della Vita e Sanità Pubblica, Università Cattolica del Sacro Cuore, Rome, Italy.,Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Rome, Italy
| | - Valentina Saccone
- Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Fondazione Santa Lucia, Rome, Italy.,Dipartimento di Scienze della Vita e Sanità Pubblica, Università Cattolica del Sacro Cuore, Rome, Italy
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21
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Li Y, Zhang J, Shi J, Liu K, Wang X, Jia Y, He T, Shen K, Wang Y, Liu J, Zhang W, Wang H, Zheng Z, Hu D. Exosomes derived from human adipose mesenchymal stem cells attenuate hypertrophic scar fibrosis by miR-192-5p/IL-17RA/Smad axis. Stem Cell Res Ther 2021; 12:221. [PMID: 33789737 PMCID: PMC8010995 DOI: 10.1186/s13287-021-02290-0] [Citation(s) in RCA: 121] [Impact Index Per Article: 30.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2021] [Accepted: 03/15/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Hypertrophic scar (HS) is a fibro-proliferative disorder of dermis after burn or trauma and usually leads to esthetic disfiguration and functionary impairment for patients. Emerging evidences demonstrated ADSC-Exo could alleviate the visceral fibrosis, but little attention had been paid to its role in skin fibrosis. In the study, we would explore the effect of ADSC-Exo on HS and investigated the exact mechanism underlying the properties. METHODS ADSC-Exo were isolated, identified, and internalized by HS-derived fibroblasts (HSFs). The effect of ADSC-Exo on the proliferation and migration of HSFs were detected by flow cytometry and Ki67 immunofluorescence staining, or scratch and trans-wells assays, respectively. RT-PCR, immunoblotting, immunofluorescence, and immunohistochemistry staining were used to evaluate the expression of IL-17RA, Col1, Col3, α-SMA, SIP1, and p-Smad2/p-Smad3 in HSFs stimulated with ADSC-Exo, miR-192-5p mimics, or inhibitors, IL-17RA siRNA and their negative controls. Digital morphology, H&E, Masson's trichrome staining, and immunohistochemistry staining were performed to measure the effect of ADSC-Exo and Lv-IL-17RA shRNA on excisional wound of BALB/c mice. RESULTS The verified ADSC-Exo effectively inhibited the proliferation and migration of HSFs, decreased the expression of Col1, Col3, α-SMA, IL-17RA, and p-Smad2/p-Smad3 and increased the levels of SIP1 in HSFs. Besides, the mice in ADSC-Exo-treated group demonstrated faster wound healing and less collagen deposition. Furthermore, miR-192-5p was highly expressed in ADSC-Exo and ADSC-Exosomal miR-192-5p ameliorated hypertrophic scar fibrosis. Meanwhile, miR-192-5p targeted the expression of IL-17RA to decrease the pro-fibrotic proteins levels. Moreover, IL-17RA was overexpressed in HS and HSFs, and knockdown IL-17RA alleviated the expression of Col1, Col3, α-SMA, and p-Smad2/p-Smad3 and increased the expression of SIP1 in HSFs. Most importantly, IL-17RA silence also facilitated wound healing, attenuated collagen production, and modulated Smad pathway in HSFs. CONCLUSIONS This study illustrated ADSC-Exo attenuated the deposition of collagen, the trans-differentiation of fibroblasts-to-myofibroblasts, and the formation of hypertrophic scar by in vitro and in vivo experiments. ADSC-Exosomal miR-192-5p targeted IL-17RA to regulate Smad pathway in hypertrophic scar fibrosis. ADSC-Exo could be a promising therapeutic strategy for clinical treatment of hypertrophic scar and the anti-fibrotic properties could be achieved by miR-192-5p/IL-17RA/Smad axis.
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Affiliation(s)
- Yan Li
- Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, 127 West Chang-le Road, Xi'an, 710032, Shaanxi, China
| | - Jian Zhang
- Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, 127 West Chang-le Road, Xi'an, 710032, Shaanxi, China
| | - Jihong Shi
- Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, 127 West Chang-le Road, Xi'an, 710032, Shaanxi, China
| | - Kaituo Liu
- Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, 127 West Chang-le Road, Xi'an, 710032, Shaanxi, China
| | - Xujie Wang
- Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, 127 West Chang-le Road, Xi'an, 710032, Shaanxi, China
| | - Yanhui Jia
- Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, 127 West Chang-le Road, Xi'an, 710032, Shaanxi, China
| | - Ting He
- Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, 127 West Chang-le Road, Xi'an, 710032, Shaanxi, China
| | - Kuo Shen
- Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, 127 West Chang-le Road, Xi'an, 710032, Shaanxi, China
| | - Yunchuan Wang
- Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, 127 West Chang-le Road, Xi'an, 710032, Shaanxi, China
| | - Jiaqi Liu
- Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, 127 West Chang-le Road, Xi'an, 710032, Shaanxi, China
| | - Wei Zhang
- Department of Plastics and Aesthetic Surgery, The First Affiliated Hospital of Xi'an Medical University, No.48 West Fenghao Road, Xi'an, 710077, Shaanxi, China
| | - Hongtao Wang
- Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, 127 West Chang-le Road, Xi'an, 710032, Shaanxi, China.
| | - Zhao Zheng
- Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, 127 West Chang-le Road, Xi'an, 710032, Shaanxi, China.
| | - Dahai Hu
- Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, 127 West Chang-le Road, Xi'an, 710032, Shaanxi, China.
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22
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Could cold plasma act synergistically with allogeneic mesenchymal stem cells to improve wound skin regeneration in a large size animal model? Res Vet Sci 2021; 136:97-110. [PMID: 33596495 DOI: 10.1016/j.rvsc.2021.01.019] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2020] [Revised: 01/05/2021] [Accepted: 01/24/2021] [Indexed: 02/06/2023]
Abstract
Skin wound healing may sometimes lead to open sores that persist for long periods and expensive hospitalization is needed. Among different kinds of therapeutic innovative approaches, mesenchymal stem cells (MSCs) and low-temperature atmospheric pressure cold plasma (ionized gas) have been recently tested to improve this regenerative process. To optimize wound healing the present study intended to combine, for the first time, these two novel approaches in a large size animal wound healing model with the aim of assessing the putative dual beneficial effects. Based on clinical, histopathological, and molecular results a synergistic action in a second intention healing wound in sheep has been observed. Experimental wounds treated with cold plasma and MSCs showed a slower but more effective healing compared to the single treatment, as observed in previous studies. The combined treatment improved the correct development of skin appendages and structural proteins of the dermis showing the potential of the dual combination as a safe and effective tool for skin regeneration in the veterinary clinical field.
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23
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Efficacy and Mode of Action of Mesenchymal Stem Cells in Non-Ischemic Dilated Cardiomyopathy: A Systematic Review. Biomedicines 2020; 8:biomedicines8120570. [PMID: 33291410 PMCID: PMC7762005 DOI: 10.3390/biomedicines8120570] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Revised: 12/02/2020] [Accepted: 12/03/2020] [Indexed: 02/06/2023] Open
Abstract
Non-ischemic dilated cardiomyopathy (NIDCM) constitutes one of the most common causes to non-ischemic heart failure. Despite treatment, the disease often progresses, causing severe morbidity and mortality, making novel treatment strategies necessary. Due to the regenerative actions of mesenchymal stem cells (MSCs), they have been proposed as a treatment for NIDCM. This systematic review aims to evaluate efficacy and mode of action (MoA) of MSC-based therapies in NIDCM. A systematic literature search was conducted in Medline (Pubmed) and Embase. A total of 27 studies were included (3 clinical trials and 24 preclinical studies). MSCs from different tissues and routes of delivery were reported, with bone marrow-derived MSCs and direct intramyocardial injections being the most frequent. All included clinical trials and 22 preclinical trials reported an improvement in cardiac function following MSC treatment. Furthermore, preclinical studies demonstrated alterations in tissue structure, gene, and protein expression patterns, primarily related to fibrosis and angiogenesis. Consequently, MSC treatment can improve cardiac function in NIDCM patients. The MoA underlying this effect involves anti-fibrosis, angiogenesis, immunomodulation, and anti-apoptosis, though these processes seem to be interdependent. These encouraging results calls for larger confirmatory clinical studies, as well as preclinical studies utilizing unbiased investigation of the potential MoA.
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24
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He X, Zhang J, Luo L, Shi J, Hu D. New Progress of Adipose-derived Stem Cells in the Therapy of Hypertrophic Scars. Curr Stem Cell Res Ther 2020; 15:77-85. [PMID: 31483236 DOI: 10.2174/1574888x14666190904125800] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2018] [Revised: 11/01/2018] [Accepted: 07/10/2019] [Indexed: 12/30/2022]
Abstract
Burns are a global public health issue of great concern. The formation of scars after burns and physical dysfunction of patients remain major challenges in the treatment of scars. Regenerative medicine based on cell therapy has become a hot topic in this century. Adipose-derived stem cells (ADSCs) play an important role in cellular therapy and have become a promising source of regenerative medicine and wound repair transplantation. However, the anti-scarring mechanism of ADSCs is still unclear yet. With the widespread application of ADSCs in medical, we firmly believe that it will bring great benefits to patients with hypertrophic scars.
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Affiliation(s)
- Xiang He
- Department of Burns and Cutaneous Surgery, Xijing Hospital, the Fourth Military Medical University, Xi' an, Shaanxi, China
| | - Julei Zhang
- Department of Burns and Cutaneous Surgery, Xijing Hospital, the Fourth Military Medical University, Xi' an, Shaanxi, China
| | - Liang Luo
- Department of Burns and Cutaneous Surgery, Xijing Hospital, the Fourth Military Medical University, Xi' an, Shaanxi, China
| | - Jihong Shi
- Department of Burns and Cutaneous Surgery, Xijing Hospital, the Fourth Military Medical University, Xi' an, Shaanxi, China
| | - Dahai Hu
- Department of Burns and Cutaneous Surgery, Xijing Hospital, the Fourth Military Medical University, Xi' an, Shaanxi, China
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25
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Deng J, Zhong L, Zhou Z, Gu C, Huang X, Shen L, Cao S, Ren Z, Zuo Z, Deng J, Yu S. Autophagy: a promising therapeutic target for improving mesenchymal stem cell biological functions. Mol Cell Biochem 2020; 476:1135-1149. [PMID: 33196943 DOI: 10.1007/s11010-020-03978-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2020] [Accepted: 11/06/2020] [Indexed: 12/13/2022]
Abstract
Mesenchymal stem cells (MSCs) are considered to be a promising therapeutic material due to their capacities for self-renewal, multilineage differentiation, and immunomodulation and have attracted great attention in regenerative medicine. However, MSCs may lose their biological functions because of donor age or disease and environmental pressure before and after transplantation, which hinders the application of MSC-based therapy. As a major intracellular lysosome-dependent degradative process, autophagy plays a pivotal role in maintaining cellular homeostasis and withstanding environmental pressure and may become a potential therapeutic target for improving MSC functions. Recent studies have demonstrated that the regulation of autophagy is a promising approach for improving the biological properties of MSCs. More in-depth investigations about the role of autophagy in MSC biology are required to contribute to the clinical application of MSCs. In this review, we focus on the role of autophagy regulation by various physical and chemical factors on the biological functions of MSCs in vitro and in vivo, and provide some strategies for enhancing the therapeutic efficacy of MSCs.
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Affiliation(s)
- Jiaqiang Deng
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
| | - Lijun Zhong
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
| | - Zihan Zhou
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
| | - Congwei Gu
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China.,Laboratory Animal Centre, Southwest Medical University, Luzhou, China
| | - Xiaoya Huang
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
| | - Liuhong Shen
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
| | - Suizhong Cao
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
| | - Zhihua Ren
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
| | - Zhicai Zuo
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
| | - Junliang Deng
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
| | - Shumin Yu
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China.
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26
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Ma J, Yan X, Lin Y, Tan Q. Hepatocyte Growth Factor Secreted from Human Adipose-Derived Stem Cells Inhibits Fibrosis in Hypertrophic Scar Fibroblasts. Curr Mol Med 2020; 20:558-571. [PMID: 31903876 DOI: 10.2174/1566524020666200106095745] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2019] [Revised: 12/18/2019] [Accepted: 12/20/2019] [Indexed: 11/22/2022]
Abstract
AIMS To study the effect of Adipose-derived stem cells (ADSCs) on fibrosis of hypertrophic scar-derived fibroblasts (HSFs) and its concrete mechanism. BACKGROUND ADSCs have been reported to reduce collagen production and fibroblast proliferation in co-culture experiments. Conditioned medium from adipose-derived stem cells (ADSCs-CM) has successfully inhibited fibrosis by decreasing the expression of collagen type І (Col1) and α-smooth muscle actin (α-SMA) in rabbit ear scar models. Hepatocyte growth factor (HGF), the primary growth factor in ADSCs-CM, has been shown to reverse fibrosis in various fibrotic diseases. OBJECTIVE To test the hypothesis that ADSCs inhibit fibrosis of HSFs through the secretion of HGF. METHODS HSFs were treated with DMEM containing 0%, 10%, 50% and 100% concentration of ADSCs-CM. The effect of ADSCs-CM on the viability was determined by cell viability assay, and the collagen production in HSFs was examined by Sirius red staining. Expression and secretion of fibrosis and degradation proteins were detected separately. After measuring the concentration of HGF in ADSCs-CM, the same number of HSFs were treated with 50% ADSCs-CM or HGF. HGF activity in ADSCs-CM was neutralized with a goat anti-human HGF antibody. RESULTS The results demonstrated that ADSCs-CM dose-dependently decreased cell viability, expression of fibrosis molecules, and tissue inhibitor of metalloproteinases-1 (TIMP-1), and significantly increased matrix metalloproteinase-1 (MMP-1) expression in HSFs. Collagen production and the ratio of collagen type І and type III (Col1/Col3) were also suppressed by ADSCs-CM in a dose-dependent manner. When HSFs were cultured with either 50% ADSCs-CM or HGF (1 ng/ml), a similar trend was observed in gene expression and protein secretion. Adding an HGF antibody to both groups returned protein expression and secretion to basal levels but did not significantly affect the fibrosis factors in the control group. CONCLUSION Our findings revealed that adipose-derived stem cell-secreted HGF effectively inhibits fibrosis-related factors and regulates extracellular matrix (ECM) remodeling in hypertrophic scar fibroblasts.
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Affiliation(s)
- Ji Ma
- 1Department of Burns and Plastic Surgery, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210008, China
| | - Xin Yan
- Department of Burns and Plastic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, China
| | - Yue Lin
- Department of Burns and Plastic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, China
| | - Qian Tan
- 1Department of Burns and Plastic Surgery, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210008, China
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Mokhtari B, Aboutaleb N, Nazarinia D, Nikougoftar M, Razavi Tousi SMT, Molazem M, Azadi MR. Comparison of the effects of intramyocardial and intravenous injections of human mesenchymal stem cells on cardiac regeneration after heart failure. IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES 2020; 23:879-885. [PMID: 32774809 PMCID: PMC7395194 DOI: 10.22038/ijbms.2020.40886.9660] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/03/2019] [Accepted: 02/01/2020] [Indexed: 12/12/2022]
Abstract
OBJECTIVES Existing studies have demonstrated that intravenous and intramyocardial-administrated mesenchymal stem cells (MSCs) lead to tissue repair after cardiac disorders. We compared the efficiency of both administration methods. MATERIALS AND METHODS A rat model of isoproterenol-induced heart failure (ISO-HF) was established to compare the effects of intravenous and intramyocardial-administrated MSCs on cardiac fibrosis and function. The animals were randomly assigned into six groups: i) control or normal, ii) ISO-HF (HF) iii) ISO-HF rats treated with intramyocardial administration of culture medium (HF+IM/CM), iv) ISO-HF rats treated with intravenous administration of culture medium ( HF+IV/CM), v) ISO-HF rats treated with intravenous administration of MSCs (HF+IV/MSCs), vi) ISO-HF rats treated with intramyocardial administration of MSCs ( HF+IM/MSCs). Cultured MSCs and culture medium were administrated at 4 weeks after final injection of ISO. Heart function, identification of MSCs, osteogenic differentiation, adipogenic differentiation, cardiac fibrosis and tissue damage were evaluated by echocardiography, flow-cytometery, von Kossa, oil red O, Masson's trichrome and H & E staining, respectively. RESULTS Both intravenous and intramyocardial MSCs therapy significantly improved heart function and reduced cardiac fibrosis and tissue damage (P<0.05), whereas the cultured medium had no beneficial effects. CONCLUSION In sum, our results confirm the validity of both administration methods in recovery of HF, but more future research is required.
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Affiliation(s)
- Behnaz Mokhtari
- Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran
- Department of Physiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Nahid Aboutaleb
- Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran
- Department of Physiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Donya Nazarinia
- Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran
- Department of Physiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Mahin Nikougoftar
- Medical Biotechnology Research Center, Guilan University of Medical Sciences, Rasht, Iran
| | | | - Mohammad Molazem
- Department of Veterinary Diagnostic Imaging, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
| | - Mohammad-Reza Azadi
- Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran
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28
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Vadivel S, Vincent P, Sekaran S, Visaga Ambi S, Muralidar S, Selvaraj V, Palaniappan B, Thirumalai D. Inflammation in myocardial injury- Stem cells as potential immunomodulators for myocardial regeneration and restoration. Life Sci 2020; 250:117582. [PMID: 32222465 DOI: 10.1016/j.lfs.2020.117582] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2019] [Revised: 03/14/2020] [Accepted: 03/20/2020] [Indexed: 12/11/2022]
Abstract
The ineffective immunosuppressant's and targeted strategies to neutralize inflammatory mediators have worsened the scenario of heart failure and have opened many questions for debate. Stem cell therapy has proven to be a promising approach for treating heart following myocardial infarction (MI). Adult stem cells, induced pluripotent stem cells and embryonic stem cells are possible cell types and have successfully shown to regenerate damaged myocardial tissue in pre-clinical and clinical studies. Current implications of using mesenchymal stem cells (MSCs) owing to their immunomodulatory functions and paracrine effects could serve as an effective alternative treatment option for rejuvenating the heart post MI. The major setback associated with the use of MSCs is reduced cell retention, engraftment and decreased effectiveness. With a few reports on understanding the role of inflammation and its dual effects on the structure and function of heart, this review focuses on these missing insights and further exemplifies the role of MSCs as an alternative therapy in treating the pathological consequences in myocardial infarction (MI).
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Affiliation(s)
- Sajini Vadivel
- School of Chemical and Biotechnology, SASTRA Deemed-to-be-University, Thanjavur 613 401, Tamil Nadu, India
| | - Preethi Vincent
- School of Chemical and Biotechnology, SASTRA Deemed-to-be-University, Thanjavur 613 401, Tamil Nadu, India
| | - Saravanan Sekaran
- School of Chemical and Biotechnology, SASTRA Deemed-to-be-University, Thanjavur 613 401, Tamil Nadu, India.
| | - Senthil Visaga Ambi
- School of Chemical and Biotechnology, SASTRA Deemed-to-be-University, Thanjavur 613 401, Tamil Nadu, India.
| | - Shibi Muralidar
- School of Chemical and Biotechnology, SASTRA Deemed-to-be-University, Thanjavur 613 401, Tamil Nadu, India
| | - Vimalraj Selvaraj
- Centre for Biotechnology, Anna University, Chennai 600 025, Tamil Nadu, India
| | - Balamurugan Palaniappan
- School of Chemical and Biotechnology, SASTRA Deemed-to-be-University, Thanjavur 613 401, Tamil Nadu, India
| | - Diraviyam Thirumalai
- School of Chemical and Biotechnology, SASTRA Deemed-to-be-University, Thanjavur 613 401, Tamil Nadu, India
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29
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Synthetic biology for improving cell fate decisions and tissue engineering outcomes. Emerg Top Life Sci 2019; 3:631-643. [PMID: 33523179 DOI: 10.1042/etls20190091] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Revised: 10/02/2019] [Accepted: 10/07/2019] [Indexed: 02/07/2023]
Abstract
Synthetic biology is a relatively new field of science that combines aspects of biology and engineering to create novel tools for the construction of biological systems. Using tools within synthetic biology, stem cells can then be reprogrammed and differentiated into a specified cell type. Stem cells have already proven to be largely beneficial in many different therapies and have paved the way for tissue engineering and regenerative medicine. Although scientists have made great strides in tissue engineering, there still remain many questions to be answered in regard to regeneration. Presented here is an overview of synthetic biology, common tools built within synthetic biology, and the way these tools are being used in stem cells. Specifically, this review focuses on how synthetic biologists engineer genetic circuits to dynamically control gene expression while also introducing emerging topics such as genome engineering and synthetic transcription factors. The findings mentioned in this review show the diverse use of stem cells within synthetic biology and provide a foundation for future research in tissue engineering with the use of synthetic biology tools. Overall, the work done using synthetic biology in stem cells is in its early stages, however, this early work is leading to new approaches for repairing diseased and damaged tissues and organs, and further expanding the field of tissue engineering.
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30
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Rode MP, Batti Angulski AB, Gomes FA, da Silva MM, Jeremias TDS, de Carvalho RG, Iucif Vieira DG, Oliveira LFC, Fernandes Maia L, Trentin AG, Hayashi L, de Miranda KR, de Aguiar AK, Rosa RD, Calloni GW. Carrageenan hydrogel as a scaffold for skin-derived multipotent stromal cells delivery. J Biomater Appl 2019; 33:422-434. [PMID: 30223731 DOI: 10.1177/0885328218795569] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Carrageenan is a thermoreversible polymer of natural origin widely used in food and pharmaceutical industry that presents a glycosaminoglycan-like structure. Herein, we show that kappa-type carrageenan extracted by a semi-refined process from the red seaweed Kappaphycus alvarezii displayed both chemical and structural properties similar to a commercial carrageenan. Moreover, both extracted carrageenan hydrogel and commercial carrageenan hydrogel can serve as a scaffold for in vitro culture of human skin-derived multipotent stromal cells, demonstrating considerable potential as cell-carrier materials for cell delivery in tissue engineering. Skin-derived multipotent stromal cells cultured inside the carrageenan hydrogels showed a round shape morphology and maintained their growth and viability for at least one week in culture. Next, the effect of the extracted carrageenan hydrogel loaded with human skin-derived multipotent stromal cells was evaluated in a mouse model of full-thickness skin wound. Macroscopic and histological analyses revealed some pointed ameliorated features, such as reduced inflammatory process, faster initial recovery of wounded area, and improved extracellular matrix deposition. These results indicate that extracted carrageenan hydrogel can serve as a scaffold for in vitro growth and maintenance of human SD-MSCs, being also able to act as a delivery system of cells to wounded skin. Thus, evaluation of the properties discussed in this study contribute to a further understanding and specificities of the potential use of carrageenan hydrogel as a delivery system for several applications, further to skin wound healing.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | - Leila Hayashi
- Universidade Federal de Santa Catarina, Florianopolis, Brazil
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31
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Hu CH, Tseng YW, Lee CW, Chiou CY, Chuang SS, Yang JY, Lee OK. Combination of mesenchymal stem cell-conditioned medium and botulinum toxin type A for treating human hypertrophic scars. J Plast Reconstr Aesthet Surg 2019; 73:516-527. [PMID: 31488377 DOI: 10.1016/j.bjps.2019.07.010] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2018] [Revised: 07/06/2019] [Accepted: 07/27/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND Both mesenchymal stem cell-conditioned medium (MSC CM) and Botox have demonstrated therapeutic effects for hypertrophic scar (HS). It is unclear whether a synergistic effect occurs when these treatments are used in combination. We aimed to investigate the therapeutic effects of MSC CM and Botox alone when compared with those of a combined regimen on HS. METHODS Fibroblasts from human HS were isolated and treated with Dulbecco's modified Eagle's medium (DMEM), MSCCM, or Botox alone or a combination of MSCCM and Botox. We also used an in vivo HS-buried null mice model to investigate the efficacy of combination treatment. RESULTS The results demonstrated that the combination of MSC CM and Botox downregulated both mRNA and protein levels of type I collagen, type III collagen, and alpha-smooth muscle actin (α-SMA) in HS fibroblasts. The combined regimen also suppressed fibroblast proliferative activity, increased apoptosis, and displayed significant inhibitory effects on the contractile ability of HS fibroblasts compared to MSC CM, Botox, or DMEM alone. Using an in vivo HS-buried null mice model, significant scar weight reduction, cell apoptosis, and less α-SMA expression were observed from the combined regimen of MSC CM and Botox compared to those from the other groups. The combined regimen also significantly improved arrangement and deposition of collagen fibers. CONCLUSIONS This study demonstrates that a combination of MSC CM and Botox exhibited a significant therapeutic effect compared to monotherapy. Clinical translation of this therapy should be further considered.
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Affiliation(s)
- Ching-Hsuan Hu
- Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Chang Gung Medical College and Chang Gung University, Taoyuan, Taiwan; Institute of Clinical Medicine, and Stem cell Research Center, National Yang-Ming University,Taipei, Taiwan; Stem Cell Research Center, National Yang-Ming University, Taipei, Taiwan
| | - Yi-Wen Tseng
- Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Chang Gung Medical College and Chang Gung University, Taoyuan, Taiwan; Institute of Clinical Medicine, and Stem cell Research Center, National Yang-Ming University,Taipei, Taiwan; Stem Cell Research Center, National Yang-Ming University, Taipei, Taiwan
| | - Chien-Wei Lee
- Institute for Tissue Engineering and Regenerative Medicine, The Chinese University of Hong Kong; School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong
| | - Chih-Yung Chiou
- Institute of Clinical Medicine, and Stem cell Research Center, National Yang-Ming University,Taipei, Taiwan
| | - Shiow-Shuh Chuang
- Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Chang Gung Medical College and Chang Gung University, Taoyuan, Taiwan
| | - Jui-Yung Yang
- Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Chang Gung Medical College and Chang Gung University, Taoyuan, Taiwan
| | - Oscar K Lee
- Institute of Clinical Medicine, and Stem cell Research Center, National Yang-Ming University,Taipei, Taiwan; Stem Cell Research Center, National Yang-Ming University, Taipei, Taiwan.
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32
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Advanced drug delivery systems and artificial skin grafts for skin wound healing. Adv Drug Deliv Rev 2019; 146:209-239. [PMID: 30605737 DOI: 10.1016/j.addr.2018.12.014] [Citation(s) in RCA: 354] [Impact Index Per Article: 59.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2018] [Revised: 11/27/2018] [Accepted: 12/27/2018] [Indexed: 12/14/2022]
Abstract
Cutaneous injuries, especially chronic wounds, burns, and skin wound infection, require painstakingly long-term treatment with an immense financial burden to healthcare systems worldwide. However, clinical management of chronic wounds remains unsatisfactory in many cases. Various strategies including growth factor and gene delivery as well as cell therapy have been used to enhance the healing of non-healing wounds. Drug delivery systems across the nano, micro, and macroscales can extend half-life, improve bioavailability, optimize pharmacokinetics, and decrease dosing frequency of drugs and genes. Replacement of the damaged skin tissue with substitutes comprising cell-laden scaffold can also restore the barrier and regulatory functions of skin at the wound site. This review covers comprehensively the advanced treatment strategies to improve the quality of wound healing.
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33
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Lee TM, Harn HJ, Chiou TW, Chuang MH, Chen CH, Chuang CH, Lin PC, Lin SZ. Preconditioned adipose-derived stem cells ameliorate cardiac fibrosis by regulating macrophage polarization in infarcted rat hearts through the PI3K/STAT3 pathway. J Transl Med 2019; 99:634-647. [PMID: 30683900 DOI: 10.1038/s41374-018-0181-x] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2018] [Revised: 11/10/2018] [Accepted: 11/17/2018] [Indexed: 11/09/2022] Open
Abstract
Stem cells can modify macrophage phenotypes; however, the mechanisms remain unclear. We investigated whether n-butylidenephthalide (BP) primed adipose-derived stem cells (ADSCs) attenuated cardiac fibrosis via regulating macrophage phenotype by a PI3K/STAT3-dependent pathway in postinfarcted rats. Male Wistar rats after coronary ligation were allocated to receive either intramyocardial injection of vehicle, ADSCs (1 × 106 cells), BP-preconditioned ADSCs, (BP + lithium)-preconditioned ADSCs, (BP + LY294002)-preconditioned ADSCs, and (BP + S3I-201)-preconditioned ADSCs. ADSCs were primed for 16 h before implantation. BP-pretreated ADSCs increased the cell viability compared with naive ADSCs in the in vitro experiments. Infarct sizes were similar among the infarcted groups at the acute and chronic stages of infarction. At day 3 after infarction, post-infarction was associated with increased M1 macrophage infiltration, which was inhibited by administering naive ADSCs. Compared with naive ADSCs, BP-preconditioned ADSCs provided a significant increase of Akt and STAT3 phosphorylation, STAT3 activity, STAT3 nuclear translocation, myocardial IL-10 levels, and the percentage of M2 macrophage infiltration. The effects of BP on M2 polarization were reversed by LY294002 or S3I-201. Furthermore, the phosphorylation of both Akt and STAT3 was abolished by LY294002, whereas Akt phosphorylation was not affected following the inhibition of STAT3. The addition of lithium did not have additional effects compared with BP alone. After 4 weeks of implantation, ADSCs remained in the myocardium, and reduced fibrosis and improved cardiac function. BP-preconditioned ADSCs provided superior cardioprotection, greater ADSC engraftment, and antifibrotic effects compared with naive ADSCs. These results suggest that BP-pretreated ADSCs polarize macrophages into M2 cells more efficiently than naive ADSCs via the PI3K/STAT3 pathway.
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Affiliation(s)
- Tsung-Ming Lee
- Cardiovascular Institute, An Nan Hospital, China Medical University, Tainan, Taiwan.,Department of Medicine, China Medical University, Taichung, Taiwan
| | - Horng-Jyh Harn
- Bioinnovation Center, Tzu Chi Foundation, Hualien, Taiwan.,Department of Pathology, Buddhist Tzu Chi General Hospital, Tzu Chi University, Hualien, Taiwan
| | - Tzyy-Wen Chiou
- Department of Life Science and Graduate Institute of Biotechnology, National Dong Hwa University, Hualien, Taiwan
| | - Ming-Hsi Chuang
- Department of Technology Management, Chung Hua University, Hsinchu, Taiwan.,Gwo Xi Stem Cell Applied Technology, Hsinchu, Taiwan
| | | | | | - Po-Cheng Lin
- Gwo Xi Stem Cell Applied Technology, Hsinchu, Taiwan
| | - Shinn-Zong Lin
- Bioinnovation Center, Tzu Chi Foundation, Hualien, Taiwan. .,Department of Neurosurgery, Buddhist Tzu Chi General Hospital, Tzu Chi University, Hualien, Taiwan.
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34
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Chai CY, Song J, Tan Z, Tai IC, Zhang C, Sun S. Adipose tissue-derived stem cells inhibit hypertrophic scar (HS) fibrosis via p38/MAPK pathway. J Cell Biochem 2019; 120:4057-4064. [PMID: 30260015 DOI: 10.1002/jcb.27689] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2018] [Accepted: 08/27/2018] [Indexed: 02/05/2023]
Abstract
OBJECTIVE The current study was designed to investigate the effects and underlying mechanisms of adipose tissue-derived stem cells (ADSCs) on hypertrophic scar (HS) fibrosis. METHOD Real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot analysis were performed to detect the expression of collagen I (Col1), collagen III (Col3), and α-smooth muscle actin (α-SMA) after fibroblasts and cultured HS tissues were treated with ADSC medium. All data were analyzed by using SPSS17.0 software. Statistical analysis was performed by Student t tests. RESULTS The in vitro study showed that ADSC medium decreased the expression of Col1, Col3, and α-SMA. In addition, the protein level of p-p38 was downregulated by ADSC medium treatment in a concentration dependent manner. CONCLUSION The current study demonstrated that ADSC could decrease collagen deposition and scar formation in in vitro experiments. The regulation of the p38/MAPK signaling pathway might play an important role in the process.
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Affiliation(s)
- Chi-Yung Chai
- Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, China
| | - Junlong Song
- Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, China
| | - Zhenwei Tan
- Department of Orthopedic Sursery, West China Hospital, Chengdu, Sichuan, China
| | - I-Chun Tai
- Southern Medical Science Ltd, Kaohsiung, Taiwan ROC
| | - Chaoying Zhang
- School of Basic Medical Sciences of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Shengrong Sun
- Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, China
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35
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Mancuso P, Raman S, Glynn A, Barry F, Murphy JM. Mesenchymal Stem Cell Therapy for Osteoarthritis: The Critical Role of the Cell Secretome. Front Bioeng Biotechnol 2019; 7:9. [PMID: 30761298 PMCID: PMC6361779 DOI: 10.3389/fbioe.2019.00009] [Citation(s) in RCA: 139] [Impact Index Per Article: 23.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Accepted: 01/11/2019] [Indexed: 12/11/2022] Open
Abstract
Osteoarthritis (OA) is an inflammatory condition still lacking effective treatments. Mesenchymal stem/stromal cells (MSCs) have been successfully employed in pre-clinical models aiming to resurface the degenerated cartilage. In early-phase clinical trials, intra-articular (IA) administration of MSCs leads to pain reduction and cartilage protection or healing. However, the consistent lack of engraftment indicates that the observed effect is delivered through a "hit-and-run" mechanism, by a temporal release of paracrine molecules. MSCs express a variety of chemokines and cytokines that aid in repair of degraded tissue, restoration of normal tissue metabolism and, most importantly, counteracting inflammation. Secretion of therapeutic factors is increased upon licensing by inflammatory signals or apoptosis, induced by the host immune system. Trophic effectors are released as soluble molecules or carried by extracellular vesicles (ECVs). This review provides an overview of the functions and mechanisms of MSC-secreted molecules found to be upregulated in models of OA, whether using in vitro or in vivo models.
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Affiliation(s)
- Patrizio Mancuso
- Regenerative Medicine Institute (REMEDI), Biosciences, National University of Ireland Galway, Galway, Ireland.,Centre for Research in Medical Devices (CÚRAM), Biosciences, National University of Ireland Galway, Galway, Ireland
| | - Swarna Raman
- Regenerative Medicine Institute (REMEDI), Biosciences, National University of Ireland Galway, Galway, Ireland
| | - Aoife Glynn
- Regenerative Medicine Institute (REMEDI), Biosciences, National University of Ireland Galway, Galway, Ireland
| | - Frank Barry
- Regenerative Medicine Institute (REMEDI), Biosciences, National University of Ireland Galway, Galway, Ireland.,Centre for Research in Medical Devices (CÚRAM), Biosciences, National University of Ireland Galway, Galway, Ireland
| | - J Mary Murphy
- Regenerative Medicine Institute (REMEDI), Biosciences, National University of Ireland Galway, Galway, Ireland.,Centre for Research in Medical Devices (CÚRAM), Biosciences, National University of Ireland Galway, Galway, Ireland
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36
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Sun X, Meng H, Wan W, Xie M, Wen C. Application potential of stem/progenitor cell-derived extracellular vesicles in renal diseases. Stem Cell Res Ther 2019; 10:8. [PMID: 30616603 PMCID: PMC6323814 DOI: 10.1186/s13287-018-1097-5] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Extracellular vesicles (EVs) are nanometer-sized and membrane-bound vesicles, including exosomes and microvesicles. EVs can deliver bioactive macromolecules such as proteins, lipids, and nucleic acids, allowing intercellular communication in multicellular organisms. EVs are secreted by all cell types including stem/progenitor cells. Stem/progenitor cell-derived EVs have been identified to exert immunomodulatory effects on target cells through transferring protein molecules as well as regulatory effects on the phenotype of target cells through fusion with the target cells membrane and/or through direct endocytosis by target cells to transfer nucleic acid substances (such as mRNA, miRNA) to the target cells. In both human and animal models, the use of stem/progenitor cells (such as bone marrow mesenchymal stromal cells) has been shown to promote the recovery of kidney diseases such as acute kidney injury and chronic kidney disease. Stem/progenitor cell-derived extracellular vesicles are an important mechanism by which stem/progenitor cells might repair kidney injury. Here, this review will discuss the latest advances concerning the application potential of stem/progenitor cell-derived extracellular vesicles in renal diseases, including the aspects as follows: anti-inflammatory, proliferation-promoting and anti-apoptotic, proangiogenic, antifibrotic and renal cancer progression-promoting. Therefore, stem/progenitor cell-derived extracellular vesicles may be a promising treatment tool for renal diseases.
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Affiliation(s)
- Xiao Sun
- Division of Hematology and Tumor, Children's Medical Center, The Second Xiangya Hospital, Central South University, No.139,Renmin road, Changsha, Hunan, People's Republic of China
| | - Huanyu Meng
- Division of Hematology and Tumor, Children's Medical Center, The Second Xiangya Hospital, Central South University, No.139,Renmin road, Changsha, Hunan, People's Republic of China
| | - Wuqing Wan
- Division of Hematology and Tumor, Children's Medical Center, The Second Xiangya Hospital, Central South University, No.139,Renmin road, Changsha, Hunan, People's Republic of China
| | - Min Xie
- Division of Hematology and Tumor, Children's Medical Center, The Second Xiangya Hospital, Central South University, No.139,Renmin road, Changsha, Hunan, People's Republic of China
| | - Chuan Wen
- Division of Hematology and Tumor, Children's Medical Center, The Second Xiangya Hospital, Central South University, No.139,Renmin road, Changsha, Hunan, People's Republic of China.
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Leong YY, Ng WH, Umar Fuaad MZ, Ng CT, Ramasamy R, Lim V, Yong YK, Tan JJ. Mesenchymal stem cells facilitate cardiac differentiation in Sox2-expressing cardiac C-kit cells in coculture. J Cell Biochem 2018; 120:9104-9116. [PMID: 30548289 DOI: 10.1002/jcb.28186] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2018] [Accepted: 11/08/2018] [Indexed: 01/11/2023]
Abstract
Stem cell therapy offers hope to reconstitute injured myocardium and salvage heart from failing. A recent approach using combinations of derived Cardiac-derived c-kit expressing cells (CCs) and mesenchymal stem cells (MSCs) in transplantation improved infarcted hearts with a greater functional outcome, but the effects of MSCs on CCs remain to be elucidated. We used a novel two-step protocol to clonogenically amplify colony forming c-kit expressing cells from 4- to 6-week-old C57BL/6N mice. This method yielded highly proliferative and clonogenic CCs with an average population doubling time of 17.2 ± 0.2, of which 80% were at the G1 phase. We identified two distinctly different CC populations based on its Sox2 expression, which was found to inversely related to their nkx2.5 and gata4 expression. To study CCs after MSC coculture, we developed micron-sized particles of iron oxide-based magnetic reisolation method to separate CCs from MSCs for subsequent analysis. Through validation using the sex and species mismatch CC-MSC coculture method, we confirmed that the purity of the reisolated cells was greater than 85%. In coculture experiment, we found that MSCs prominently enhanced Ctni and Mef2c expressions in Sox2 pos CCs after the induction of cardiac differentiation, and the level was higher than that of conditioned medium Sox2 pos CCs. However, these effects were not found in Sox2 neg CCs. Immunofluorescence labeling confirmed the presence of cardiac-like cells within Sox2 pos CCs after differentiation, identified by its cardiac troponin I and α-sarcomeric actinin expressions. In conclusion, this study shows that MSCs enhance CC differentiation toward cardiac myocytes. This enhancement is dependent on CC stemness state, which is determined by Sox2 expression.
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Affiliation(s)
- Yin Yee Leong
- Regenerative Medicine Cluster, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Kepala Batas, Penang, Malaysia
| | - Wai Hoe Ng
- Regenerative Medicine Cluster, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Kepala Batas, Penang, Malaysia
| | - Mimi Zulaikha Umar Fuaad
- Regenerative Medicine Cluster, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Kepala Batas, Penang, Malaysia
| | - Chin Theng Ng
- Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.,Department of Preclinical, Physiology Unit, Faculty of Medicine, AIMST University, Bedong, Kedah, Malaysia
| | - Rajesh Ramasamy
- Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia
| | - Vuanghao Lim
- Regenerative Medicine Cluster, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Kepala Batas, Penang, Malaysia
| | - Yoke Keong Yong
- Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia
| | - Jun Jie Tan
- Regenerative Medicine Cluster, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Kepala Batas, Penang, Malaysia
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Chen J, Wei J, Huang Y, Ma Y, Ni J, Li M, Zhu Y, Gao X, Fan G. Danhong Injection Enhances the Therapeutic Efficacy of Mesenchymal Stem Cells in Myocardial Infarction by Promoting Angiogenesis. Front Physiol 2018; 9:991. [PMID: 30093864 PMCID: PMC6070728 DOI: 10.3389/fphys.2018.00991] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2017] [Accepted: 07/06/2018] [Indexed: 01/07/2023] Open
Abstract
Stem cell-based therapies have the potential to dramatically transform the treatment and prognosis of myocardial infarction (MI), and mesenchymal stem cells (MSCs) have been suggested as a promising cell population to ameliorate the heart remodeling in post-MI. However, poor implantation and survival in ischemic myocardium restrict its efficacy and application. In this study, we sought to use the unique mode of action of Chinese medicine to improve this situation. Surrounding the myocardial infarct area, we performed a multi-point MSC transplantation and administered in conjunction with Danhong injection, which is mainly used for the treatment of MI. Our results showed that the MSC survival rate and cardiac function were improved significantly through the small animal imaging system and echocardiography, respectively. Moreover, histological analysis showed that MSC combined with DHI intervention significantly reduced myocardial infarct size in myocardial infarcted mice and significantly increased MSC resident. To investigate the mechanism of DHI promoting MSC survival and cell migration, PCR and WB experiments were performed. Our results showed that DHI could promote the expression of CXC chemokine receptor 4 in MSC and enhance the expression of stromal cell–derived factor-1 in myocardium, and this effect can be inhibited by AMD3100 (an SDF1/CXCR4 antagonist). Additionally, MSC in combination with DHI interfered with MI in mice and this signifies that when combined, the duo could the expression of vascular endothelial growth factor (VEGF) in the marginal zone of infarction compared with when either MSC or DHI are used individually. Based on these results, we conclude that DHI enhances the residence of MSCs in cardiac tissue by modulating the SDF1/CXCR4 signaling pathway. These findings have important therapeutic implications for Chinese medicine-assisted cell-based therapy strategies.
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Affiliation(s)
- Jingrui Chen
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Jing Wei
- Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Yuting Huang
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Yuling Ma
- Oxford Chinese Medicine Research Centre, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom
| | - Jingyu Ni
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Min Li
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Yan Zhu
- Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Xiumei Gao
- Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Guanwei Fan
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
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39
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Exosomal miR-21a-5p mediates cardioprotection by mesenchymal stem cells. J Mol Cell Cardiol 2018; 119:125-137. [DOI: 10.1016/j.yjmcc.2018.04.012] [Citation(s) in RCA: 110] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2017] [Revised: 04/02/2018] [Accepted: 04/21/2018] [Indexed: 12/22/2022]
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40
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Hegab MH, Abd-Allah SH, Badawey MS, Saleh AA, Metwally AS, Fathy GM, Nada SM, Abdel-Rahman SA, Saleh AA, Fawzy A, El-Magd MA. Therapeutic potential effect of bone marrow-derived mesenchymal stem cells on chronic liver disease in murine Schistosomiasis Mansoni. J Parasit Dis 2018; 42:277-286. [PMID: 29844633 DOI: 10.1007/s12639-018-0997-8] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2018] [Accepted: 04/11/2018] [Indexed: 12/11/2022] Open
Abstract
Some reports have shown that mesenchymal stem cells (MSCs) therapy could ameliorate chemically-induced hepatic fibrosis. This research assesses the therapeutic action of bone marrow mesenchymal stem cells (BM-MSCs) on chronic diseased liver in Schistosoma mansoni infected mice. All infected female mice divided into three groups, one group (15 mice) treated with oral praziquantel (PZQ), second group (15 mice) received intravenous injection of BM-MSCs and third group (15 mice) treated with both MSCs + PZQ. Two control groups (15 mice each) subdivided into one infected and second healthy one. BM-MSCs were obtained from bones of both femur and tibia of male mice (30 mice), then cultured and characterized morphologically by detection of CD105 by flow cytometer. Liver tissues for all groups were examined histopathologically. Measuring of the collagen 1 gene expression was done by real-time PCR and immunohistochemical study to detect stem cells differentiation for detection of MSCs engraftments in liver tissue. MSCs treatment caused marked improvement and regression of fibrosis, and prevents deposition of collagen and reduced the expression of collagen 1 gene in infected mice on their liver tissues, especially when used with PZQ in mice treatment. It can be concluded that, MSCs is a good therapeutic method for liver fibrosis caused by S. mansoni infection.
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Affiliation(s)
- Mohamed H Hegab
- 1Department of Parasitology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Somia H Abd-Allah
- 2Department of Biochemistry, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Maha S Badawey
- 1Department of Parasitology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Ayman A Saleh
- 3Department of Animal Wealth Development, Genetics & Genetic Engineering, of Veterinary Medicine, Zagazig University, Zagazig, Egypt
| | - Ashraf S Metwally
- 1Department of Parasitology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Ghada M Fathy
- 1Department of Parasitology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Soad M Nada
- 1Department of Parasitology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Sara A Abdel-Rahman
- 1Department of Parasitology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Amira A Saleh
- 1Department of Parasitology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Amal Fawzy
- 2Department of Biochemistry, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Mohammed Abu El-Magd
- 4Department of Anatomy & Embryology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh, Egypt
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41
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Si H, Zhang Y, Song Y, Li L. Overexpression of adrenomedullin protects mesenchymal stem cells against hypoxia and serum deprivation‑induced apoptosis via the Akt/GSK3β and Bcl‑2 signaling pathways. Int J Mol Med 2018; 41:3342-3352. [PMID: 29512737 PMCID: PMC5881801 DOI: 10.3892/ijmm.2018.3533] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2016] [Accepted: 02/02/2018] [Indexed: 01/12/2023] Open
Abstract
The poor survival rate of transplanted mesenchymal stem cells (MSCs) within the ischemic heart limits their therapeutic potential for cardiac repair. Adrenomedullin (ADM) has been identified as a potent apoptotic inhibitor. The present study aimed to investigate the protective effects of ADM on MSCs against hypoxia and serum deprivation (H/SD)‑induced apoptosis, and to determine the potential underlying mechanisms. In the present study, a recombinant adenovirus expressing the ADM gene was established and was infected into MSCs. The infection rate was determined via microscopic detection of green fluorescence and flow cytometric analysis. The mRNA expression levels of ADM were detected by reverse transcription‑polymerase chain reaction. In addition, a model of H/SD was generated. The MSCs were randomly separated into six groups: Control, enhanced green fluorescent protein (EGFP)‑Adv, EGFP‑ADM, H/SD, EGFP‑Adv + H/SD and EGFP‑ADM + H/SD. Cell viability and proliferation were determined using the Cell Counting kit‑8 assay. Apoptosis was assessed by terminal deoxynucleotidyl transferase‑mediated‑dUTP nick‑end labeling assay and flow cytometric analysis using Annexin V‑phycoerythrin/7‑aminoactinomycin D staining. The protein expression levels of total protein kinase B (Akt), phosphorylated (p)‑Akt, total glycogen synthase kinase (GSK)3β, p‑GSK3β, B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax), caspase‑3 and cleaved caspase‑3 were detected by western blot analysis. The results indicated that ADM overexpression could improve MSC proliferation and viability, and protect MSCs against H/SD‑induced apoptosis. In addition, ADM overexpression increased Akt and GSK3β phosphorylation, and Bcl‑2/Bax ratio, and decreased the activation of caspase‑3. These results suggested that ADM protects MSCs against H/SD‑induced apoptosis, which may be mediated via the Akt/GSK3β and Bcl‑2 signaling pathways.
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Affiliation(s)
- Hongjin Si
- The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Harbin, Heilongjiang 150086, P.R. China
| | - Yao Zhang
- The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Harbin, Heilongjiang 150086, P.R. China
| | - Yuqing Song
- The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Harbin, Heilongjiang 150086, P.R. China
| | - Lili Li
- The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Harbin, Heilongjiang 150086, P.R. China
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42
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Acellular derivatives of mesenchymal stem cells prevent peritoneal adhesions in an animal model. J Surg Res 2018; 223:198-206. [DOI: 10.1016/j.jss.2017.11.018] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2017] [Revised: 10/14/2017] [Accepted: 11/03/2017] [Indexed: 12/21/2022]
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43
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Teh SW, Mok PL, Abd Rashid M, Bastion MLC, Ibrahim N, Higuchi A, Murugan K, Mariappan R, Subbiah SK. Recent Updates on Treatment of Ocular Microbial Infections by Stem Cell Therapy: A Review. Int J Mol Sci 2018; 19:ijms19020558. [PMID: 29438279 PMCID: PMC5855780 DOI: 10.3390/ijms19020558] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2017] [Revised: 12/03/2017] [Accepted: 12/12/2017] [Indexed: 02/06/2023] Open
Abstract
Ocular microbial infection has emerged as a major public health crisis during the past two decades. A variety of causative agents can cause ocular microbial infections; which are characterized by persistent and destructive inflammation of the ocular tissue; progressive visual disturbance; and may result in loss of visual function in patients if early and effective treatments are not received. The conventional therapeutic approaches to treat vision impairment and blindness resulting from microbial infections involve antimicrobial therapy to eliminate the offending pathogens or in severe cases; by surgical methods and retinal prosthesis replacing of the infected area. In cases where there is concurrent inflammation, once infection is controlled, anti-inflammatory agents are indicated to reduce ocular damage from inflammation which ensues. Despite advances in medical research; progress in the control of ocular microbial infections remains slow. The varying level of ocular tissue recovery in individuals and the incomplete visual functional restoration indicate the chief limitations of current strategies. The development of a more extensive therapy is needed to help in healing to regain vision in patients. Stem cells are multipotent stromal cells that can give rise to a vast variety of cell types following proper differentiation protocol. Stem cell therapy shows promise in reducing inflammation and repairing tissue damage on the eye caused by microbial infections by its ability to modulate immune response and promote tissue regeneration. This article reviews a selected list of common infectious agents affecting the eye; which include fungi; viruses; parasites and bacteria with the aim of discussing the current antimicrobial treatments and the associated therapeutic challenges. We also provide recent updates of the advances in stem cells studies on sepsis therapy as a suggestion of optimum treatment regime for ocular microbial infections.
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Affiliation(s)
- Seoh Wei Teh
- Department of Biomedical Science, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia.
| | - Pooi Ling Mok
- Department of Biomedical Science, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia.
- Genetics and Regenerative Medicine Research Centre, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia.
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Aljouf University, 72442 Sakaka, Aljouf Province, Saudi Arabia.
| | - Munirah Abd Rashid
- Department of Ophthalmology, Faculty of Medicine, UKM Medical Center, 56000 Cheras, Kuala Lumpur, Malaysia.
| | - Mae-Lynn Catherine Bastion
- Department of Ophthalmology, Faculty of Medicine, UKM Medical Center, 56000 Cheras, Kuala Lumpur, Malaysia.
| | - Normala Ibrahim
- Department of Psychiatry, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia.
| | - Akon Higuchi
- Department of Chemical and Materials Engineering, National Central University, No. 300, Jhongda RD., Jhongli, 32001 Taoyuan, Taiwan.
| | - Kadarkarai Murugan
- Department of Zoology, Thiruvalluvar University, Serkkadu, 632 115 Vellore, India.
| | - Rajan Mariappan
- Biomaterials in Medicinal Chemistry Laboratory, Department of Natural Products Chemistry, School of Chemistry, Madurai Kamaraj University, Madurai, 625 021 Tamil Nadu, India.
| | - Suresh Kumar Subbiah
- Genetics and Regenerative Medicine Research Centre, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia.
- Department of Medical Microbiology and Parasitology, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia.
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44
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Kim JE, Lee JH, Kim SH, Jung Y. Skin Regeneration with Self-Assembled Peptide Hydrogels Conjugated with Substance P in a Diabetic Rat Model. Tissue Eng Part A 2018; 24:21-33. [DOI: 10.1089/ten.tea.2016.0517] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023] Open
Affiliation(s)
- Ji Eun Kim
- KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, Republic of Korea
- Biomaterials Research Center, Korea Institute of Science and Technology, Seoul, Republic of Korea
| | - Jung Hwa Lee
- KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, Republic of Korea
- Biomaterials Research Center, Korea Institute of Science and Technology, Seoul, Republic of Korea
| | - Soo Hyun Kim
- KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, Republic of Korea
- Biomaterials Research Center, Korea Institute of Science and Technology, Seoul, Republic of Korea
- Department of Biomedical Engineering, University of Science and Technology (UST), Seoul, Republic of Korea
| | - Youngmee Jung
- Biomaterials Research Center, Korea Institute of Science and Technology, Seoul, Republic of Korea
- Department of Biomedical Engineering, University of Science and Technology (UST), Seoul, Republic of Korea
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45
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Cellular Therapeutics for Heart Failure: Focus on Mesenchymal Stem Cells. Stem Cells Int 2017; 2017:9640108. [PMID: 29391871 PMCID: PMC5748110 DOI: 10.1155/2017/9640108] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2017] [Revised: 07/31/2017] [Accepted: 08/14/2017] [Indexed: 12/28/2022] Open
Abstract
Resulting from a various etiologies, the most notable remains ischemia; heart failure (HF) manifests as the common end pathway of many cardiovascular processes and remains among the top causes for hospitalization and a major cause of morbidity and mortality worldwide. Current pharmacologic treatment for HF utilizes pharmacologic agents to control symptoms and slow further deterioration; however, on a cellular level, in a patient with progressive disease, fibrosis and cardiac remodeling can continue leading to end-stage heart failure. Cellular therapeutics have risen as the new hope for an improvement in the treatment of HF. Mesenchymal stem cells (MSCs) have gained popularity given their propensity of promoting endogenous cellular repair of a myriad of disease processes via paracrine signaling through expression of various cytokines, chemokines, and adhesion molecules resulting in activation of signal transduction pathways. While the exact mechanism remains to be completely elucidated, this remains the primary mechanism identified to date. Recently, MSCs have been incorporated as the central focus in clinical trials investigating the role how MSCs can play in the treatment of HF. In this review, we focus on the characteristics of MSCs that give them a distinct edge as cellular therapeutics and present results of clinical trials investigating MSCs in the setting of ischemic HF.
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46
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Li LL, Peng C, Zhang M, Liu Y, Li H, Chen H, Sun Y, Zhu C, Zhang Y. Mesenchymal stem cells overexpressing adrenomedullin improve heart function through antifibrotic action in rats experiencing heart failure. Mol Med Rep 2017; 17:1437-1444. [PMID: 29138835 PMCID: PMC5780080 DOI: 10.3892/mmr.2017.8049] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2016] [Accepted: 03/13/2017] [Indexed: 02/05/2023] Open
Abstract
Previous studies of the authors have indicated that the transplantation of mesenchymal stem cells (MSCs) can attenuate cardiac fibrosis through the secretion of antifibrotic factors, such as adrenomedullin (ADM). Therefore, the authors addressed the hypothesis that ADM overexpression could enhance the antifibrotic effect of MSCs transplantation in a rat model of heart failure. The results of the present study demonstrated that, compared with the group that received the GFP-MSCs, the transplantation of ADM-MSCs significantly improved heart function and decreased the percentage of fibrotic area and the expression of matrix metalloproteinase 2. In addition, fluorescence microscopy indicated that the survival of transplanted MSCs also increased significantly in the ADM-MSCs-treated group. Furthermore, the expression of fibrosis-related genes, such as ADM and hepatocyte growth factor, were significantly influenced in the ADM-MSCs-treated group. Based on these findings, it may be concluded that, compared with MSCs, MSCs overexpressing ADM can further improve heart function in rats experiencing heart failure through enhanced antifibrotic activity.
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Affiliation(s)
- Li Li Li
- Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China
| | - Cheng Peng
- Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China
| | - Meiling Zhang
- Department of Cardiology, The Third Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China
| | - Yumei Liu
- Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China
| | - Hefei Li
- Department of Cardiology, The Central Hospital of Handan, Handan, Hebei 056000, P.R. China
| | - Huibo Chen
- Department of Cardiology, The Second Hospital of Harbin, Harbin, Heilongjiang 150086, P.R. China
| | - Yu Sun
- Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China
| | - Chunjun Zhu
- Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China
| | - Yao Zhang
- Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China
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Jiang H, Gao Q, Che X, Zhu L, Zhang Z, Chen Y, Dai Y. Inhibition of penile tunica albuginea myofibroblasts activity by adipose-derived stem cells. Exp Ther Med 2017; 14:5149-5156. [PMID: 29201230 DOI: 10.3892/etm.2017.5179] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2017] [Accepted: 08/24/2017] [Indexed: 12/13/2022] Open
Abstract
The activation of tunica albuginea myofibroblasts (MFs) serves an essential role in Peyronie's disease (PD). Increasing evidence has reported that adipose tissue-derived stem cells (ADSCs) have been demonstrated to attenuate the symptoms of PD in animal models. However, the mechanisms of the antifibrotic effects of ADSCs in PD remain to be fully elucidated. In the present study, the inhibitory effects and possible mechanism of ADSCs on the activation of MFs derived from rat penile tunica albuginea were investigated. ADSCs were obtained from the paratesticular fat of Sprague Dawley rats. MFs were transformed from rat penile tunica albuginea fibroblasts through stimulation with 5 ng/ml tumor growth factor-β1. Transwell cell cultures were adopted for co-culture of ADSCs and MFs. Western blot analysis was used to assess changes in the expression levels of α smooth muscle actin (αSMA), collagen I, phosphorylated (p)-SMAD family member 2 (Smad2), Smad2, ras homolog family member A (RhoA), Rho associated coiled-coil containing protein kinase (ROCK)1 and ROCK2, caspase3, caspase9, and matrix metalloproteinases (MMPs). Collagen gel assays were used to assess cell contractility. Additionally, the concentration of hydroxyproline in the culture medium was detected using commercially available kits. It was demonstrated that ADSCs reduced the expression of αSMA and collagen I of MFs. Furthermore, p-Smad2, RhoA, ROCK1 and ROCK2 expression was significantly reduced in the MFs+ADSCs group compared with that in the MFs-only culture, while the expression of MMPs (MMP2, MMP3, MMP9 and MMP13) and caspases (caspase3 and caspase9) was upregulated. In addition, ADSCs were able to downregulate the concentration of hydroxyproline in the culture medium of MFs and reverse the contraction of MFs. Collectively, these results suggested that ADSCs inhibited the activation of MFs, decreased collagen production, and suppressed the contraction of myofibroblasts, via Smad and RhoA/ROCK signaling pathways. Furthermore, ADSCs reduced the deposition of collagen and promoted the apoptosis of MFs via MMPs, and caspases. Accordingly, the application of ADSCs may provide a novel therapeutic strategy for PD.
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Affiliation(s)
- Hesong Jiang
- Department of Andrology, Drum Tower Hospital, Affiliated to School of Medicine, Nanjing University, Nanjing, Jiangsu 210008, P.R. China
| | - Qingqiang Gao
- Department of Andrology, Drum Tower Hospital, Affiliated to School of Medicine, Nanjing University, Nanjing, Jiangsu 210008, P.R. China
| | - Xiaoyan Che
- Department of Andrology, Drum Tower Hospital, Affiliated to School of Medicine, Nanjing University, Nanjing, Jiangsu 210008, P.R. China
| | - Leilei Zhu
- Department of Andrology, Drum Tower Hospital, Affiliated to School of Medicine, Nanjing University, Nanjing, Jiangsu 210008, P.R. China
| | - Zheng Zhang
- Department of Andrology, Drum Tower Hospital, Affiliated to School of Medicine, Nanjing University, Nanjing, Jiangsu 210008, P.R. China
| | - Yun Chen
- Department of Andrology, Drum Tower Hospital, Affiliated to School of Medicine, Nanjing University, Nanjing, Jiangsu 210008, P.R. China
| | - Yutian Dai
- Department of Andrology, Drum Tower Hospital, Affiliated to School of Medicine, Nanjing University, Nanjing, Jiangsu 210008, P.R. China
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Eltoukhy HS, Sinha G, Moore CA, Sandiford OA, Rameshwar P. Immune modulation by a cellular network of mesenchymal stem cells and breast cancer cell subsets: Implication for cancer therapy. Cell Immunol 2017; 326:33-41. [PMID: 28779846 DOI: 10.1016/j.cellimm.2017.07.011] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2017] [Revised: 07/28/2017] [Accepted: 07/29/2017] [Indexed: 02/07/2023]
Abstract
The immune modulatory properties of mesenchymal stem cells (MSCs) are mostly controlled by the particular microenvironment. Cancer stem cells (CSCs), which can initiate a clinical tumor, have been the subject of intense research. This review article discusses investigative studies of the roles of MSCs on cancer biology including on CSCs, and the potential as drug delivery to tumors. An understanding of how MSCs behave in the tumor microenvironment to facilitate the survival of tumor cells would be crucial to identify drug targets. More importantly, since CSCs survive for decades in dormancy for later resurgence, studies are presented to show how MSCs could be involved in maintaining dormancy. Although the mechanism by which CSCs survive is complex, this article focus on the cellular involvement of MSCs with regard to immune responses. We discuss the immunomodulatory mechanisms of MSC-CSC interaction in the context of therapeutic outcomes in oncology. We also discuss immunotherapy as a potential to circumventing this immune modulation.
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Affiliation(s)
- Hussam S Eltoukhy
- Rutgers, New Jersey Medical School, Department of Medicine-Hematology-Oncology, Newark, NJ 07103, USA
| | - Garima Sinha
- Rutgers, New Jersey Medical School, Department of Medicine-Hematology-Oncology, Newark, NJ 07103, USA
| | - Caitlyn A Moore
- Rutgers, New Jersey Medical School, Department of Medicine-Hematology-Oncology, Newark, NJ 07103, USA
| | - Oleta A Sandiford
- Rutgers, New Jersey Medical School, Department of Medicine-Hematology-Oncology, Newark, NJ 07103, USA
| | - Pranela Rameshwar
- Rutgers, New Jersey Medical School, Department of Medicine-Hematology-Oncology, Newark, NJ 07103, USA.
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Goradel NH, Hour FG, Negahdari B, Malekshahi ZV, Hashemzehi M, Masoudifar A, Mirzaei H. Stem Cell Therapy: A New Therapeutic Option for Cardiovascular Diseases. J Cell Biochem 2017; 119:95-104. [PMID: 28543595 DOI: 10.1002/jcb.26169] [Citation(s) in RCA: 116] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2017] [Accepted: 05/24/2017] [Indexed: 12/12/2022]
Abstract
Cardiovascular diseases are known as one of major causes of morbidity and mortality worldwide. Despite the many advancement in therapies are associated with cardiovascular diseases, it seems that finding of new therapeutic option is necessary. Cell therapy is one of attractive therapeutic platforms for treatment of a variety of diseases such as cardiovascular diseases. Among of various types of cell therapy, stem cell therapy has been emerged as an effective therapeutic approach in this area. Stem cells divided into multipotent stem cells and pluripotent stem cells. A large number studies indicated that utilization of each of them are associated with a variety of advantages and disadvantages. Multiple lines evidence indicated that stem cell therapy could be used as suitable therapeutic approach for treatment of cardiovascular diseases. Many clinical trials have been performed for assessing efficiency of stem cell therapies in human. However, stem cell therapy are associated with some challenges, but, it seems resolving of them could contribute to using of them as effective therapeutic approach for patients who suffering from cardiovascular diseases. In the current review, we summarized current therapeutic strategies based on stem cells for cardiovascular diseases. J. Cell. Biochem. 119: 95-104, 2018. © 2017 Wiley Periodicals, Inc.
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Affiliation(s)
- Nasser Hashemi Goradel
- Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Farshid Ghiyami- Hour
- Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Babak Negahdari
- Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Ziba Vaisi Malekshahi
- Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Milad Hashemzehi
- Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Aria Masoudifar
- Department of Molecular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran
| | - Hamed Mirzaei
- Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
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50
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Li L, Guan Q, Dai S, Wei W, Zhang Y. Integrin β1 Increases Stem Cell Survival and Cardiac Function after Myocardial Infarction. Front Pharmacol 2017; 8:135. [PMID: 28367125 PMCID: PMC5355448 DOI: 10.3389/fphar.2017.00135] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2016] [Accepted: 03/03/2017] [Indexed: 12/27/2022] Open
Abstract
Bone mesenchymal stem cells (BMSCs) transplantation is a promising therapeutic approach for myocardial infarction (MI), but its application is limited by poor viability of BMSCs. In this study, we aimed to improve the survival of BMSCs by lentivirus vector mediated overexpression of integrin β1. In vitro study showed that integrin β1 overexpression could facilitate the proliferation of BMSCs under oxygen glucose deprivation condition and regulated the expression of Caspase-3, Bax, Bcl-2, FAK, and ILK in BMSCs. Next, MI was induced in rat model and Igtb1BMSCs, NullBMSCs, or NatBMSCs were transplanted by intramyocardial injection. One week later, the survival of BMSCs was higher in Itgb1 BMSCs group than in other groups. Four weeks after transplantation, heart function was significantly improved in Igtb1BMSCs group compared to other groups. The expression levels of Caspase-3 and Bax were decreased while the expression levels of Bcl-2, FAK, ILK, and VEGF were increased in the cardiomyocytes of Igtb1BMSCs group compared to other groups. In conclusion, integrin β1 overexpression could increase the survival of BMSCs and improve the efficacy of transplanted BMSCs for MI treatment. The beneficial effects may be mediated by inhibiting the apoptosis of both transplanted BMSCs and cardiomyocytes through adhesion-mediated cell survival signaling.
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Affiliation(s)
- Lili Li
- Department of Cardiology, The Second Affiliated Hospital, Harbin Medical University Harbin, China
| | - Qifan Guan
- Department of Cardiology, Yunnan Fuwai Cardiovascular Disease Hospital Kunming City, China
| | - Shuling Dai
- Department of Cardiac Rehabilitation, Shanxi Cardiovascular Hospital Taiyuan City, China
| | - Wen Wei
- Department of Paediatrics, The First Affiliated Hospital, Harbin Medical University Harbin, China
| | - Yao Zhang
- Department of Cardiology, The Second Affiliated Hospital, Harbin Medical University Harbin, China
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