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Galhom RA, Ali SNS, El-Fark MMO, Ali MHM, Hussein HH. Assessment of therapeutic efficacy of adipose tissue-derived mesenchymal stem cells administration in hyperlipidemia-induced aortic atherosclerosis in adult male albino rats. Tissue Cell 2024; 90:102498. [PMID: 39079452 DOI: 10.1016/j.tice.2024.102498] [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: 06/20/2024] [Revised: 07/21/2024] [Accepted: 07/24/2024] [Indexed: 09/03/2024]
Abstract
Atherosclerosis (AS) is a common disease seriously detrimental to human health. AS is a chronic progressive disease related to inflammatory reactions. The present study aimed to characterize and evaluate the effects of adipose tissue stem cells (ADSCs) in high-fat diet-induced atherosclerosis in a rat model. The present study comprises thirty-six rats and they were divided into three groups: the control group, the high-fat diet (HFD) group; which received a high-fat diet, and the high-fat diet + stem cells (HFD+SC) group; which was fed with a high-fat diet along with the administration of intravenous ADSCs. Food was given to the animals for 20 weeks to establish dyslipidemia models. After 20 weeks, animals were sacrificed by cervical dislocation; blood was collected to measure total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL); aortae were collected to detect morphologic changes. Rats of the HFD group showed a significant increase in body weight (B.Wt), altered lipid profile increased expression of inducible nitric oxide synthase (iNOS), and decreased expression of endothelial nitric oxide synthase (eNOS). However, in HFD+SC there was a significant decrease in body weight gain and an improvement in lipid profile. Histopathological and ultrastructural variations observed in the aorta of the HFD group when treated with ADSCs showed preserved normal histological architecture and reduced atherosclerosis compared with the HFD group. This was evidenced by laboratory, histological, immunohistochemical, and morphometric studies. Thus, ADSCs reduced TC, TG, and LDL, reduced the expression of iNOS, and increased the expression of eNOS. The high-fat diet was likely to cause damage to the wall of blood vessels. Systemically transplanted ADSCs could home to the aorta, and further protect the aorta from HFD-induced damage.
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Affiliation(s)
- Rania A Galhom
- Department of Human Anatomy and Embryology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt; Department of Human Anatomy and Embryology, Faculty of Medicine, Badr University in Cairo (BUC), Egypt.
| | - Saleh Nasser Saleh Ali
- Department of Human Anatomy and Embryology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt; Department of Human Anatomy and Embryology, Faculty of Medicine and Health Sciences, Thamar University, Thamar, Yemen.
| | - Magdy Mohamed Omar El-Fark
- Department of Human Anatomy and Embryology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
| | - Mona Hassan Mohammed Ali
- Department of Human Anatomy and Embryology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
| | - Hoda Hassan Hussein
- Department of Human Anatomy and Embryology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
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Li XL, Fan W, Fan B. Dental pulp regeneration strategies: A review of status quo and recent advances. Bioact Mater 2024; 38:258-275. [PMID: 38745589 PMCID: PMC11090883 DOI: 10.1016/j.bioactmat.2024.04.031] [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: 11/27/2023] [Revised: 02/18/2024] [Accepted: 04/28/2024] [Indexed: 05/16/2024] Open
Abstract
Microorganisms, physical factors such as temperature or mechanical injury, and chemical factors such as free monomers from composite resin are the main causes of dental pulp diseases. Current clinical treatment methods for pulp diseases include the root canal therapy, vital pulp therapy and regenerative endodontic therapy. Regenerative endodontic therapy serves the purpose of inducing the regeneration of new functional pulp tissues through autologous revascularization or pulp tissue engineering. This article first discusses the current clinical methods and reviews strategies as well as the research outcomes regarding the pulp regeneration. Then the in vivo models, the prospects and challenges for regenerative endodontic therapy were further discussed.
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Affiliation(s)
- Xin-Lu Li
- The State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, 237 Luoyu Road, 430079, Wuhan, China
| | - Wei Fan
- The State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, 237 Luoyu Road, 430079, Wuhan, China
| | - Bing Fan
- The State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, 237 Luoyu Road, 430079, Wuhan, China
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3
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Li L, Zhang X, Wu Y, Xing C, Du H. Challenges of mesenchymal stem cells in the clinical treatment of COVID-19. Cell Tissue Res 2024; 396:293-312. [PMID: 38512548 DOI: 10.1007/s00441-024-03881-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2023] [Accepted: 02/19/2024] [Indexed: 03/23/2024]
Abstract
The 2019 coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has brought an enormous public health burden to the global society. The duration of the epidemic, the number of infected people, and the widespread of the epidemic are extremely rare in modern society. In the initial stage of infection, people generally show fever, cough, and dyspnea, which can lead to pneumonia, acute respiratory syndrome, kidney failure, and even death in severe cases. The strong infectivity and pathogenicity of SARS-CoV-2 make it more urgent to find an effective treatment. Mesenchymal stem cells (MSCs) are a kind of pluripotent stem cells with the potential for self-renewal and multi-directional differentiation. They are widely used in clinical experiments because of their low immunogenicity and immunomodulatory function. Mesenchymal stem cell-derived exosomes (MSC-Exo) can play a physiological role similar to that of stem cells. Since the COVID-19 pandemic, a series of clinical trials based on MSC therapy have been carried out. The results show that MSCs are safe and can significantly improve patients' respiratory function and prognosis of COVID-19. Here, the effects of MSCs and MSC-Exo in the treatment of COVID-19 are reviewed, and the clinical challenges that may be faced in the future are clarified.
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Affiliation(s)
- Luping Li
- School of Chemistry and Biological Engineering, University of Science and Technology Beijing, No. 30 XueYuan Road, Haidian District, Beijing, 100083, China
- Daxing Research Institute, University of Science and Technology Beijing, Beijing, 100083, China
| | - Xiaoshuang Zhang
- School of Chemistry and Biological Engineering, University of Science and Technology Beijing, No. 30 XueYuan Road, Haidian District, Beijing, 100083, China
- Daxing Research Institute, University of Science and Technology Beijing, Beijing, 100083, China
| | - Yawen Wu
- School of Chemistry and Biological Engineering, University of Science and Technology Beijing, No. 30 XueYuan Road, Haidian District, Beijing, 100083, China
- Daxing Research Institute, University of Science and Technology Beijing, Beijing, 100083, China
| | - Cencan Xing
- Daxing Research Institute, University of Science and Technology Beijing, Beijing, 100083, China.
| | - Hongwu Du
- School of Chemistry and Biological Engineering, University of Science and Technology Beijing, No. 30 XueYuan Road, Haidian District, Beijing, 100083, China.
- Daxing Research Institute, University of Science and Technology Beijing, Beijing, 100083, China.
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He J, Liu B, Du X, Wei Y, Kong D, Feng B, Guo R, Asiamah EA, Griffin MD, Hynes SO, Shen S, Liu Y, Cui H, Ma J, O'Brien T. Amelioration of diabetic nephropathy in mice by a single intravenous injection of human mesenchymal stromal cells at early and later disease stages is associated with restoration of autophagy. Stem Cell Res Ther 2024; 15:66. [PMID: 38443965 PMCID: PMC10916232 DOI: 10.1186/s13287-024-03647-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2023] [Accepted: 01/24/2024] [Indexed: 03/07/2024] Open
Abstract
BACKGROUND AND AIMS Mesenchymal stromal cells (MSCs) a potentially effective disease-modulating therapy for diabetic nephropathy (DN) but their clinical translation has been hampered by incomplete understanding of the optimal timing of administration and in vivo mechanisms of action. This study aimed to elucidate the reno-protective potency and associated mechanisms of single intravenous injections of human umbilical cord-derived MSCs (hUC-MSCs) following shorter and longer durations of diabetes. METHODS A streptozotocin (STZ)-induced model of diabetes and DN was established in C57BL/6 mice. In groups of diabetic animals, human (h)UC-MSCs or vehicle were injected intravenously at 8 or 16 weeks after STZ along with vehicle-injected non-diabetic animals. Diabetes-related kidney abnormalities was analyzed 2 weeks later by urine and serum biochemical assays, histology, transmission electron microscopy and immunohistochemistry. Serum concentrations of pro-inflammatory and pro-fibrotic cytokines were quantified by ELISA. The expression of autophagy-related proteins within the renal cortices was investigated by immunoblotting. Bio-distribution of hUC-MSCs in kidney and other organs was evaluated in diabetic mice by injection of fluorescent-labelled cells. RESULTS Compared to non-diabetic controls, diabetic mice had increases in urine albumin creatinine ratio (uACR), mesangial matrix deposition, podocyte foot process effacement, glomerular basement membrane thickening and interstitial fibrosis as well as reduced podocyte numbers at both 10 and 18 weeks after STZ. Early (8 weeks) hUC-MSC injection was associated with reduced uACR and improvements in multiple glomerular and renal interstitial abnormalities as well as reduced serum IL-6, TNF-α, and TGF-β1 compared to vehicle-injected animals. Later (16 weeks) hUC-MSC injection also resulted in reduction of diabetes-associated renal abnormalities and serum TGF-β1 but not of serum IL-6 and TNF-α. At both time-points, the kidneys of vehicle-injected diabetic mice had higher ratio of p-mTOR to mTOR, increased abundance of p62, lower abundance of ULK1 and Atg12, and reduced ratio of LC3B to LC3A compared to non-diabetic animals, consistent with diabetes-associated suppression of autophagy. These changes were largely reversed in the kidneys of hUC-MSC-injected mice. In contrast, neither early nor later hUC-MSC injection had effects on blood glucose and body weight of diabetic animals. Small numbers of CM-Dil-labeled hUC-MSCs remained detectable in kidneys, lungs and liver of diabetic mice at 14 days after intravenous injection. CONCLUSIONS Single intravenous injections of hUC-MSCs ameliorated glomerular abnormalities and interstitial fibrosis in a mouse model of STZ-induced diabetes without affecting hyperglycemia, whether administered at relatively short or longer duration of diabetes. At both time-points, the reno-protective effects of hUC-MSCs were associated with reduced circulating TGF-β1 and restoration of intra-renal autophagy.
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Affiliation(s)
- Jingjing He
- Hebei Medical University-University of Galway Stem Cell Research Center, Hebei Medical University, Shijiazhuang, 050017, Hebei Province, China
- Hebei Research Center for Stem Cell Medical Translational Engineering, Shijiazhuang, 050017, Hebei Province, China
- Hebei Technology Innovation Center for Stem Cell and Regenerative Medicine, Shijiazhuang, 050017, Hebei Province, China
- Hebei International Joint Research Center for Stem Cell and Regenerative Medicine, Shijiazhuang, 050017, Hebei Province, China
| | - Boxin Liu
- Hebei Medical University-University of Galway Stem Cell Research Center, Hebei Medical University, Shijiazhuang, 050017, Hebei Province, China
- Hebei Research Center for Stem Cell Medical Translational Engineering, Shijiazhuang, 050017, Hebei Province, China
- Hebei Technology Innovation Center for Stem Cell and Regenerative Medicine, Shijiazhuang, 050017, Hebei Province, China
- Hebei International Joint Research Center for Stem Cell and Regenerative Medicine, Shijiazhuang, 050017, Hebei Province, China
| | - Xiaofeng Du
- Hebei Medical University-University of Galway Stem Cell Research Center, Hebei Medical University, Shijiazhuang, 050017, Hebei Province, China
- Hebei Research Center for Stem Cell Medical Translational Engineering, Shijiazhuang, 050017, Hebei Province, China
- Hebei Technology Innovation Center for Stem Cell and Regenerative Medicine, Shijiazhuang, 050017, Hebei Province, China
- Hebei International Joint Research Center for Stem Cell and Regenerative Medicine, Shijiazhuang, 050017, Hebei Province, China
| | - Yan Wei
- Hebei Medical University-University of Galway Stem Cell Research Center, Hebei Medical University, Shijiazhuang, 050017, Hebei Province, China
- Hebei Research Center for Stem Cell Medical Translational Engineering, Shijiazhuang, 050017, Hebei Province, China
- Hebei Technology Innovation Center for Stem Cell and Regenerative Medicine, Shijiazhuang, 050017, Hebei Province, China
- Hebei International Joint Research Center for Stem Cell and Regenerative Medicine, Shijiazhuang, 050017, Hebei Province, China
| | - Desheng Kong
- Hebei Medical University-University of Galway Stem Cell Research Center, Hebei Medical University, Shijiazhuang, 050017, Hebei Province, China
- Hebei Research Center for Stem Cell Medical Translational Engineering, Shijiazhuang, 050017, Hebei Province, China
- Hebei Technology Innovation Center for Stem Cell and Regenerative Medicine, Shijiazhuang, 050017, Hebei Province, China
- Hebei International Joint Research Center for Stem Cell and Regenerative Medicine, Shijiazhuang, 050017, Hebei Province, China
| | - Baofeng Feng
- Hebei Medical University-University of Galway Stem Cell Research Center, Hebei Medical University, Shijiazhuang, 050017, Hebei Province, China
- Hebei Research Center for Stem Cell Medical Translational Engineering, Shijiazhuang, 050017, Hebei Province, China
- Hebei Technology Innovation Center for Stem Cell and Regenerative Medicine, Shijiazhuang, 050017, Hebei Province, China
- Hebei International Joint Research Center for Stem Cell and Regenerative Medicine, Shijiazhuang, 050017, Hebei Province, China
- Human Anatomy Department, Hebei Medical University, Shijiazhuang, 050017, Hebei Province, China
| | - Ruiyun Guo
- Hebei Medical University-University of Galway Stem Cell Research Center, Hebei Medical University, Shijiazhuang, 050017, Hebei Province, China
- Hebei Research Center for Stem Cell Medical Translational Engineering, Shijiazhuang, 050017, Hebei Province, China
- Hebei Technology Innovation Center for Stem Cell and Regenerative Medicine, Shijiazhuang, 050017, Hebei Province, China
- Hebei International Joint Research Center for Stem Cell and Regenerative Medicine, Shijiazhuang, 050017, Hebei Province, China
| | - Ernest Amponsah Asiamah
- Hebei Medical University-University of Galway Stem Cell Research Center, Hebei Medical University, Shijiazhuang, 050017, Hebei Province, China
- Hebei Research Center for Stem Cell Medical Translational Engineering, Shijiazhuang, 050017, Hebei Province, China
- Hebei Technology Innovation Center for Stem Cell and Regenerative Medicine, Shijiazhuang, 050017, Hebei Province, China
- Hebei International Joint Research Center for Stem Cell and Regenerative Medicine, Shijiazhuang, 050017, Hebei Province, China
- Department of Forensic Sciences, College of Agriculture and Natural Sciences, University of Cape Coast, PMB UCC, Cape Coast, Ghana
| | - Matthew D Griffin
- Hebei Medical University-University of Galway Stem Cell Research Center, Hebei Medical University, Shijiazhuang, 050017, Hebei Province, China
- Regenerative Medicine Institute (REMEDI) at CÚRAM SFI Research Centre for Medical Devices, School of Medicine, University of Galway, Galway, Ireland
| | - Sean O Hynes
- Discipline of Pathology, School of Medicine, University of Galway, Galway, Ireland
| | - Sanbing Shen
- Hebei Medical University-University of Galway Stem Cell Research Center, Hebei Medical University, Shijiazhuang, 050017, Hebei Province, China
- Regenerative Medicine Institute (REMEDI) at CÚRAM SFI Research Centre for Medical Devices, School of Medicine, University of Galway, Galway, Ireland
| | - Yan Liu
- Department of Endocrinology, Hebei Medical University Third Affiliated Hospital, Shijiazhuang, 050051, Hebei, China
| | - Huixian Cui
- Hebei Medical University-University of Galway Stem Cell Research Center, Hebei Medical University, Shijiazhuang, 050017, Hebei Province, China
- Hebei Research Center for Stem Cell Medical Translational Engineering, Shijiazhuang, 050017, Hebei Province, China
- Hebei Technology Innovation Center for Stem Cell and Regenerative Medicine, Shijiazhuang, 050017, Hebei Province, China
- Hebei International Joint Research Center for Stem Cell and Regenerative Medicine, Shijiazhuang, 050017, Hebei Province, China
- Human Anatomy Department, Hebei Medical University, Shijiazhuang, 050017, Hebei Province, China
| | - Jun Ma
- Hebei Medical University-University of Galway Stem Cell Research Center, Hebei Medical University, Shijiazhuang, 050017, Hebei Province, China.
- Hebei Research Center for Stem Cell Medical Translational Engineering, Shijiazhuang, 050017, Hebei Province, China.
- Hebei Technology Innovation Center for Stem Cell and Regenerative Medicine, Shijiazhuang, 050017, Hebei Province, China.
- Hebei International Joint Research Center for Stem Cell and Regenerative Medicine, Shijiazhuang, 050017, Hebei Province, China.
- Human Anatomy Department, Hebei Medical University, Shijiazhuang, 050017, Hebei Province, China.
| | - Timothy O'Brien
- Hebei Medical University-University of Galway Stem Cell Research Center, Hebei Medical University, Shijiazhuang, 050017, Hebei Province, China.
- Regenerative Medicine Institute (REMEDI) at CÚRAM SFI Research Centre for Medical Devices, School of Medicine, University of Galway, Galway, Ireland.
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Chin SP, Marzuki M, Tai L, Mohamed Shahrehan NA, Ricky C, Fanty A, Salleh A, Low CT, Then KY, Hoe SLL, Cheong SK. Dynamic tracking of human umbilical cord mesenchymal stem cells (hUC-MSCs) following intravenous administration in mice model. Regen Ther 2024; 25:273-283. [PMID: 38314402 PMCID: PMC10834363 DOI: 10.1016/j.reth.2024.01.003] [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: 11/30/2023] [Revised: 01/07/2024] [Accepted: 01/18/2024] [Indexed: 02/06/2024] Open
Abstract
Introduction In the past decades, human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have sparked interest in cellular therapy due to their immunomodulatory properties. Nevertheless, the fate of hUC-MSCs in the body remains poorly understood. This study aimed to investigate the biodistribution, homing and clearance of systemically administered hUC-MSCs in healthy BALB/c mice model. Methods hUC-MSCs were labelled with GFP-Luc2 protein, followed by characterisation with flow cytometry. Upon intravenous infusion of transduced hUC-MSCs into the healthy BALB/c mice, the cells were dynamically monitored through the bioluminescent imaging (BLI) approach. Results Transduction of hUC-MSCs with GFP-Luc2 not only preserved the characteristics of MSCs, but also allowed live monitoring of transduced cells in the mice model. Upon systemic administration, BLI showed that transduced hUC-MSCs first localised predominantly in the lungs of healthy BALB/c mice and mainly remained in the lungs for up to 3 days before eventually cleared from the body. At terminal sacrifice, plasma chemistry biomarkers remained unchanged except for C-peptide levels, which were significantly reduced in the hUC-MSCs group. Histopathological findings further revealed that hUC-MSCs infusion did not cause any adverse effects and toxicity to lung, liver and heart tissues. Conclusions Collectively, systemically administrated hUC-MSCs was safe and demonstrated dynamic homing capacity before eventually disappearing from the body.
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Affiliation(s)
- Sze-Piaw Chin
- Cytopeutics Sdn Bhd, Cyberjaya, Selangor, Malaysia
- M. Kandiah Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Sungai Long, Selangor, Malaysia
| | - Marini Marzuki
- Molecular Pathology Unit, Cancer Research Centre, Institute for Medical Research, NIH, Setia Alam, Selangor, Malaysia
| | - Lihui Tai
- Cytopeutics Sdn Bhd, Cyberjaya, Selangor, Malaysia
| | | | - Christine Ricky
- Molecular Pathology Unit, Cancer Research Centre, Institute for Medical Research, NIH, Setia Alam, Selangor, Malaysia
| | - Audrey Fanty
- Molecular Pathology Unit, Cancer Research Centre, Institute for Medical Research, NIH, Setia Alam, Selangor, Malaysia
| | - Annas Salleh
- Department of Veterinary Laboratory Diagnosis, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang, Selangor, Malaysia
| | - Chui Thean Low
- Molecular Pathology Unit, Cancer Research Centre, Institute for Medical Research, NIH, Setia Alam, Selangor, Malaysia
| | | | - Susan Ling Ling Hoe
- Molecular Pathology Unit, Cancer Research Centre, Institute for Medical Research, NIH, Setia Alam, Selangor, Malaysia
| | - Soon Keng Cheong
- M. Kandiah Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Sungai Long, Selangor, Malaysia
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Tao H, Lv Q, Zhang J, Chen L, Yang Y, Sun W. Different Levels of Autophagy Activity in Mesenchymal Stem Cells Are Involved in the Progression of Idiopathic Pulmonary Fibrosis. Stem Cells Int 2024; 2024:3429565. [PMID: 38390035 PMCID: PMC10883747 DOI: 10.1155/2024/3429565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Revised: 11/17/2023] [Accepted: 02/03/2024] [Indexed: 02/24/2024] Open
Abstract
Idiopathic pulmonary fibrosis (IPF) is an age-related lung interstitial disease that occurs predominantly in people over 65 years of age and for which there is a lack of effective therapeutic agents. It has demonstrated that mesenchymal stem cells (MSCs) including alveolar epithelial cells (AECs) can perform repair functions. However, MSCs lose their repair functions due to their distinctive aging characteristics, eventually leading to the progression of IPF. Recent breakthroughs have revealed that the degree of autophagic activity influences the renewal and aging of MSCs and determines the prognosis of IPF. Autophagy is a lysosome-dependent pathway that mediates the degradation and recycling of intracellular material and is an efficient way to renew the nonnuclear (cytoplasmic) part of eukaryotic cells, which is essential for maintaining cellular homeostasis and is a potential target for regulating MSCs function. Therefore, this review focuses on the changes in autophagic activity of MSCs, clarifies the relationship between autophagy and health status of MSCs and the effect of autophagic activity on MSCs senescence and IPF, providing a theoretical basis for promoting the clinical application of MSCs.
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Affiliation(s)
- Hongxia Tao
- School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Qin Lv
- Department of Respiratory and Critical Medicine, Sichuan Provincial People's Hospital, Sichuan Academy of Medical Sciences, Chengdu, Sichuan, China
- Medical College, University of Electronic Science and Technology, Chengdu, China
| | - Jing Zhang
- Department of Respiratory and Critical Medicine, Sichuan Provincial People's Hospital, Sichuan Academy of Medical Sciences, Chengdu, Sichuan, China
- Medical College, University of Electronic Science and Technology, Chengdu, China
| | - Lijuan Chen
- Department of Respiratory and Critical Medicine, Sichuan Provincial People's Hospital, Sichuan Academy of Medical Sciences, Chengdu, Sichuan, China
- Medical College, University of Electronic Science and Technology, Chengdu, China
| | - Yang Yang
- Department of Respiratory and Critical Medicine, Sichuan Provincial People's Hospital, Sichuan Academy of Medical Sciences, Chengdu, Sichuan, China
- Medical College, University of Electronic Science and Technology, Chengdu, China
| | - Wei Sun
- Department of Respiratory and Critical Medicine, Sichuan Provincial People's Hospital, Sichuan Academy of Medical Sciences, Chengdu, Sichuan, China
- Medical College, University of Electronic Science and Technology, Chengdu, China
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Li J, Wu Z, Zhao L, Liu Y, Su Y, Gong X, Liu F, Zhang L. The heterogeneity of mesenchymal stem cells: an important issue to be addressed in cell therapy. Stem Cell Res Ther 2023; 14:381. [PMID: 38124129 PMCID: PMC10734083 DOI: 10.1186/s13287-023-03587-y] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Accepted: 11/24/2023] [Indexed: 12/23/2023] Open
Abstract
With the continuous improvement of human technology, the medical field has gradually moved from molecular therapy to cellular therapy. As a safe and effective therapeutic tool, cell therapy has successfully created a research boom in the modern medical field. Mesenchymal stem cells (MSCs) are derived from early mesoderm and have high self-renewal and multidirectional differentiation ability, and have become one of the important cores of cell therapy research by virtue of their immunomodulatory and tissue repair capabilities. In recent years, the application of MSCs in various diseases has received widespread attention, but there are still various problems in the treatment of MSCs, among which the heterogeneity of MSCs may be one of the causes of the problem. In this paper, we review the correlation of MSCs heterogeneity to provide a basis for further reduction of MSCs heterogeneity and standardization of MSCs and hope to provide a reference for cell therapy.
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Affiliation(s)
- Jingxuan Li
- Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, China
| | - Zewen Wu
- Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, China
| | - Li Zhao
- School of Pharmacy, Shanxi Medical University, Taiyuan, 030600, China
| | - Yang Liu
- Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, China
| | - Yazhen Su
- Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, China
| | - Xueyan Gong
- Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, China
| | - Fancheng Liu
- Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, China
| | - Liyun Zhang
- Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, China.
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8
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Galgaro BC, Beckenkamp LR, Naasani LIS, Wink MR. Adenosine metabolism by mesenchymal stromal cells isolated from different human tissues. Hum Cell 2023; 36:2247-2258. [PMID: 37535223 DOI: 10.1007/s13577-023-00957-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Accepted: 07/18/2023] [Indexed: 08/04/2023]
Abstract
Mesenchymal stromal cells (MSCs) have unique biological properties and play important functions, which make them attractive tools for cell-based therapies. The basic mechanisms of these cells are not fully understood. However, the adenosinergic pathway contributes to the main effects attributed to MSCs. Adenosine is a highly immunosuppressive molecule and exerts a central role in inflammation by neutralizing the proinflammatory ATP influence. This nucleoside is produced by purinergic signaling, an important physiological pathway for MSCs, which involves proliferation, migration, differentiation, and apoptosis. Therefore, in this study, we analyzed the extracellular AMP hydrolysis and consequent adenosine production, as well as the expression of CD73 and adenosine receptors on the cell surface of MSCs isolated from different human tissues: dermis (D-MSCs), adipose tissue (AD-MSCs), and umbilical cord (UC-MSCs). All cells confirmed their multipotent capacity by adipogenic, osteogenic, and chondrogenic differentiation, as well as the expression of cell surface markers including CD44 + , CD105 + , and CD90 + . All MSCs expressed similar levels of CD73 and CD26 without a statistical difference among the different tissues, whereas ADA expression was lower in AD-MSCs. In addition, A1R and A3R mRNA levels were higher in D-MSCs and AD-MSCs, respectively. Enzymatic assay showed that AD-MSCs have the highest hydrolysis rate of AMP, leading to increased amount of adenosine production. Moreover, despite all MSCs completely hydrolyze extracellular AMP generating adenosine, the pattern of nucleosides metabolism was different. Therefore, although MSCs share certain characteristics as the multilineage potential and immunophenotype, they show different adenosinergic profiles according to tissue origin.
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Affiliation(s)
- Bruna Campos Galgaro
- Laboratório de Biologia Celular, Universidade Federal de Ciências da Saúde de Porto Alegre, UFCSPA, Rua Sarmento Leite, 245, Porto Alegre, RS, CEP 90050-170, Brazil
| | - Liziane Raquel Beckenkamp
- Laboratório de Biologia Celular, Universidade Federal de Ciências da Saúde de Porto Alegre, UFCSPA, Rua Sarmento Leite, 245, Porto Alegre, RS, CEP 90050-170, Brazil
| | - Liliana I Sous Naasani
- Laboratório de Biologia Celular, Universidade Federal de Ciências da Saúde de Porto Alegre, UFCSPA, Rua Sarmento Leite, 245, Porto Alegre, RS, CEP 90050-170, Brazil
| | - Márcia Rosângela Wink
- Laboratório de Biologia Celular, Universidade Federal de Ciências da Saúde de Porto Alegre, UFCSPA, Rua Sarmento Leite, 245, Porto Alegre, RS, CEP 90050-170, Brazil.
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9
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Xu W, Yang Y, Li N, Hua J. Interaction between Mesenchymal Stem Cells and Immune Cells during Bone Injury Repair. Int J Mol Sci 2023; 24:14484. [PMID: 37833933 PMCID: PMC10572976 DOI: 10.3390/ijms241914484] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Revised: 09/13/2023] [Accepted: 09/19/2023] [Indexed: 10/15/2023] Open
Abstract
Fractures are the most common large organ trauma in humans. The initial inflammatory response promotes bone healing during the initial post-fracture phase, but chronic and persistent inflammation due to infection or other factors does not contribute to the healing process. The precise mechanisms by which immune cells and their cytokines are regulated in bone healing remain unclear. The use of mesenchymal stem cells (MSCs) for cellular therapy of bone injuries is a novel clinical treatment approach. Bone progenitor MSCs not only differentiate into bone, but also interact with the immune system to promote the healing process. We review in vitro and in vivo studies on the role of the immune system and bone marrow MSCs in bone healing and their interactions. A deeper understanding of this paradigm may provide clues to potential therapeutic targets in the healing process, thereby improving the reliability and safety of clinical applications of MSCs to promote bone healing.
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Affiliation(s)
| | | | - Na Li
- Shaanxi Centre of Stem Cells Engineering & Technology, College of Veterinary Medicine, Northwest A&F University, Yangling, Xianyang 712100, China; (W.X.); (Y.Y.)
| | - Jinlian Hua
- Shaanxi Centre of Stem Cells Engineering & Technology, College of Veterinary Medicine, Northwest A&F University, Yangling, Xianyang 712100, China; (W.X.); (Y.Y.)
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10
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Wang Z, Huang M, Zhang Y, Jiang X, Xu L. Comparison of Biological Properties and Clinical Application of Mesenchymal Stem Cells from the Mesoderm and Ectoderm. Stem Cells Int 2023; 2023:4547875. [PMID: 37333060 PMCID: PMC10276766 DOI: 10.1155/2023/4547875] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Revised: 05/04/2023] [Accepted: 05/23/2023] [Indexed: 06/20/2023] Open
Abstract
Since the discovery of mesenchymal stem cells (MSCs) in the 1970s, they have been widely used in the treatment of a variety of diseases because of their wide sources, strong differentiation potential, rapid expansion in vitro, low immunogenicity, and so on. At present, most of the related research is on mesoderm-derived MSCs (M-MSCs) such as bone marrow MSCs and adipose-derived MSCs. As a type of MSC, ectoderm-derived MSCs (E-MSCs) have a stronger potential for self-renewal, multidirectional differentiation, and immunomodulation and have more advantages than M-MSCs in some specific conditions. This paper analyzes the relevant research development of E-MSCs compared with that of M-MSCs; summarizes the extraction, discrimination and culture, biological characteristics, and clinical application of E-MSCs; and discusses the application prospects of E-MSCs. This summary provides a theoretical basis for the better application of MSCs from both ectoderm and mesoderm in the future.
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Affiliation(s)
- Zhenning Wang
- Medical School of Chinese PLA, Beijing 100853, China
- Department of Orthodontics, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Meng Huang
- Medical School of Chinese PLA, Beijing 100853, China
- Department of Orthodontics, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Yu Zhang
- Medical School of Chinese PLA, Beijing 100853, China
- Department of Orthodontics, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Xiaoxia Jiang
- Beijing Institute of Basic Medical Sciences, Beijing 100850, China
| | - Lulu Xu
- Department of Orthodontics, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
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11
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Vignon C, Hilpert M, Toupet K, Goubaud A, Noël D, de Kalbermatten M, Hénon P, Jorgensen C, Barbero A, Garitaonandia I. Evaluation of expanded peripheral blood derived CD34+ cells for the treatment of moderate knee osteoarthritis. Front Bioeng Biotechnol 2023; 11:1150522. [PMID: 37288358 PMCID: PMC10242004 DOI: 10.3389/fbioe.2023.1150522] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2023] [Accepted: 04/04/2023] [Indexed: 06/09/2023] Open
Abstract
Knee osteoarthritis (OA) is a degenerative joint disease of the knee that results from the progressive loss of articular cartilage. It is most common in the elderly and affects millions of people worldwide, leading to a continuous increase in the number of total knee replacement surgeries. These surgeries improve the patient's physical mobility, but can lead to late infection, loosening of the prosthesis, and persistent pain. We would like to investigate if cell-based therapies can avoid or delay such surgeries in patients with moderate OA by injecting expanded autologous peripheral blood derived CD34+ cells (ProtheraCytes®) into the articular joint. In this study we evaluated the survival of ProtheraCytes® when exposed to synovial fluid and their performance in vitro with a model consisting of their co-culture with human OA chondrocytes in separate layers of Transwells and in vivo with a murine model of OA. Here we show that ProtheraCytes® maintain high viability (>95%) when exposed for up to 96 hours to synovial fluid from OA patients. Additionally, when co-cultured with OA chondrocytes, ProtheraCytes® can modulate the expression of some chondrogenic (collagen II and Sox9) and inflammatory/degrading (IL1β, TNF, and MMP-13) markers at gene or protein levels. Finally, ProtheraCytes® survive after injection into the knee of a collagenase-induced osteoarthritis mouse model, engrafting mainly in the synovial membrane, probably due to the fact that ProtheraCytes® express CD44, a receptor of hyaluronic acid, which is abundantly present in the synovial membrane. This report provides preliminary evidence of the therapeutic potential of CD34+ cells on OA chondrocytes in vitro and their survival after in vivo implantation in the knee of mice and merits further investigation in future preclinical studies in OA models.
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Affiliation(s)
| | - Morgane Hilpert
- Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Karine Toupet
- Institute of Regenerative Medicine and Biotherapy, University of Montpellier, INSERM, Montpellier, France
| | | | - Danièle Noël
- Institute of Regenerative Medicine and Biotherapy, University of Montpellier, INSERM, Montpellier, France
| | | | | | - Christian Jorgensen
- Institute of Regenerative Medicine and Biotherapy, University of Montpellier, INSERM, Montpellier, France
| | - Andrea Barbero
- Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland
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12
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Barachini S, Biso L, Kolachalam S, Petrini I, Maggio R, Scarselli M, Longoni B. Mesenchymal Stem Cell in Pancreatic Islet Transplantation. Biomedicines 2023; 11:biomedicines11051426. [PMID: 37239097 DOI: 10.3390/biomedicines11051426] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Revised: 05/02/2023] [Accepted: 05/08/2023] [Indexed: 05/28/2023] Open
Abstract
Pancreatic islet transplantation is a therapeutic option for achieving physiologic regulation of plasma glucose in Type 1 diabetic patients. At the same time, mesenchymal stem cells (MSCs) have demonstrated their potential in controlling graft rejection, the most fearsome complication in organ/tissue transplantation. MSCs can interact with innate and adaptive immune system cells either through direct cell-cell contact or through their secretome including exosomes. In this review, we discuss current findings regarding the graft microenvironment of pancreatic islet recipient patients and the crucial role of MSCs operation as cell managers able to control the immune system to prevent rejection and promote endogenous repair. We also discuss how challenging stressors, such as oxidative stress and impaired vasculogenesis, may jeopardize graft outcomes. In order to face these adverse conditions, we consider either hypoxia-exposure preconditioning of MSCs or human stem cells with angiogenic potential in organoids to overcome islets' lack of vasculature. Along with the shepherding of carbon nanotubes-loaded MSCs to the transplantation site by a magnetic field, these studies look forward to exploiting MSCs stemness and their immunomodulatory properties in pancreatic islet transplantation.
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Affiliation(s)
- Serena Barachini
- Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy
| | - Letizia Biso
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy
| | - Shivakumar Kolachalam
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy
- Aseptic Pharmacy, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London W6 8RF, UK
| | - Iacopo Petrini
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy
| | - Roberto Maggio
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, 67100 L'Aquila, Italy
| | - Marco Scarselli
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy
| | - Biancamaria Longoni
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy
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13
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Sabet Sarvestani F, Tamaddon AM, Yaghoobi R, Geramizadeh B, Abolmaali SS, Kaviani M, Keshtkar S, Pakbaz S, Azarpira N. Indirect co-culture of islet cells in 3D biocompatible collagen/laminin scaffold with angiomiRs transfected mesenchymal stem cells. Cell Biochem Funct 2023; 41:296-308. [PMID: 36815688 DOI: 10.1002/cbf.3781] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Revised: 02/05/2023] [Accepted: 02/06/2023] [Indexed: 02/24/2023]
Abstract
Diabetes is an autoimmune disease in which the pancreatic islets produce insufficient insulin. One of the treatment strategies is islet isolation, which may damage these cells as they lack vasculature. Biocompatible scaffolds are one of the efficient techniques for dealing with this issue. The current study is aimed to determine the effect of transfected BM-MSCS with angiomiR-126 and -210 on the survival and functionality of islets loaded into a 3D scaffold via laminin (LMN). AngiomiRs/Poly Ethylenimine polyplexes were transfected into bone marrow-mesenchymal stem cells (BM-MSCs), followed by 3-day indirect co-culturing with islets laden in collagen (Col)-based hydrogel scaffolds containing LMN. Islet proliferation and viability were significantly increased in LMN-containing scaffolds, particularly in the miRNA-126 treated group. Insulin gene expression was superior in Col scaffolds, especially, in the BM-MSCs/miRNA-126 treated group. VEGF was upregulated in the LMN-containing scaffolds in both miRNA-treated groups, specifically in the miRNA-210, leading to VEGF secretion. MiRNAs' target genes showed no downregulation in LMN-free scaffolds; while a drastic downregulation was seen in the LMN-containing scaffolds. The highest insulin secretion was recorded in the Oxidized dextran (Odex)/ColLMN+ group with miRNA-126. LMN-containing biocompatible scaffolds, once combined with angiomiRs and their downstream effectors, promote islets survival and restore function, leading to enhanced angiogenesis and glycemic status.
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Affiliation(s)
| | - Ali-Mohammad Tamaddon
- Department of Pharmaceutical Nanotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Islamic Republic of Iran, Shiraz, Iran.,Center for Nanotechnology in Drug Delivery, Shiraz University of Medical Sciences, Shiraz, Islamic Republic of Iran, Shiraz, Iran
| | - Ramin Yaghoobi
- Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Bita Geramizadeh
- Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Samira Sadat Abolmaali
- Department of Pharmaceutical Nanotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Islamic Republic of Iran, Shiraz, Iran
| | - Maryam Kaviani
- Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Somayeh Keshtkar
- Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.,Molecular Dermatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Sara Pakbaz
- Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.,Department of Laboratory Medicine & Pathobiology, Mount Sinai Hospital, Toronto, Ontario, Canada
| | - Negar Azarpira
- Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
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14
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Velasco MG, Satué K, Chicharro D, Martins E, Torres-Torrillas M, Peláez P, Miguel-Pastor L, Del Romero A, Damiá E, Cuervo B, Carrillo JM, Cugat R, Sopena JJ, Rubio M. Multilineage-Differentiating Stress-Enduring Cells (Muse Cells): The Future of Human and Veterinary Regenerative Medicine. Biomedicines 2023; 11:biomedicines11020636. [PMID: 36831171 PMCID: PMC9953712 DOI: 10.3390/biomedicines11020636] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 02/13/2023] [Accepted: 02/17/2023] [Indexed: 02/22/2023] Open
Abstract
In recent years, several studies have been conducted on Muse cells mainly due to their pluripotency, high tolerance to stress, self-renewal capacity, ability to repair DNA damage and not being tumoral. Additionally, since these stem cells can be isolated from different tissues in the adult organism, obtaining them is not considered an ethical problem, providing an advantage over embryonic stem cells. Regarding their therapeutic potential, few studies have reported clinical applications in the treatment of different diseases, such as aortic aneurysm and chondral injuries in the mouse or acute myocardial infarction in the swine, rabbit, sheep and in humans. This review aims to describe the characterization of Muse cells, show their biological characteristics, explain the differences between Muse cells and mesenchymal stem cells, and present their contribution to the treatment of some diseases.
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Affiliation(s)
- María Gemma Velasco
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain
| | - Katy Satué
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain
| | - Deborah Chicharro
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain
| | - Emma Martins
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain
| | - Marta Torres-Torrillas
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain
| | - Pau Peláez
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain
| | - Laura Miguel-Pastor
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain
| | - Ayla Del Romero
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain
| | - Elena Damiá
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain
| | - Belén Cuervo
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain
| | - José María Carrillo
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain
- Garcia Cugat Foundation CEU-UCH Chair of Medicine and Regenerative Surgery, 08006 Barcelona, Spain
| | - Ramón Cugat
- Garcia Cugat Foundation CEU-UCH Chair of Medicine and Regenerative Surgery, 08006 Barcelona, Spain
| | - Joaquín Jesús Sopena
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain
- Garcia Cugat Foundation CEU-UCH Chair of Medicine and Regenerative Surgery, 08006 Barcelona, Spain
- Correspondence:
| | - Mónica Rubio
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain
- Garcia Cugat Foundation CEU-UCH Chair of Medicine and Regenerative Surgery, 08006 Barcelona, Spain
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15
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Mishra PJ, Banerjee D. Visualizing Activated Myofibroblasts Resulting from Differentiation of Mesenchymal Stem Cells. Methods Mol Biol 2022; 2593:83-92. [PMID: 36513925 DOI: 10.1007/978-1-0716-2811-9_5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Mesenchymal stem cells (MSCs) are multipotent cells that exhibit two main characteristics which define stem cells: self-renewal and differentiation. MSCs can migrate to sites of injury, inflammation, and tumor. Moreover, MSCs undergo myofibroblast-like differentiation, including increased production of α-SMA in response to transforming growth factor-β (TGF-β), a growth factor commonly secreted by tumor cells to evade immune surveillance. Based on our previous findings, hMSCs become activated and resemble carcinoma-associated myofibroblasts upon prolonged exposure to a conditioned medium from MDAMB231 human breast cancer cells. In this section, we show using immunofluorescence that keratinocyte-conditioned medium (KCM) induces differentiation of MSCs to resemble dermal myofibroblast-like cells with punctate vinculin staining and F-actin filaments.
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Affiliation(s)
- Pravin J Mishra
- Department of Pharmacology, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, Piscataway, NJ, USA
| | - Debabrata Banerjee
- Department of Pharmacology, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.
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16
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Neural Regeneration in Regenerative Endodontic Treatment: An Overview and Current Trends. Int J Mol Sci 2022; 23:ijms232415492. [PMID: 36555133 PMCID: PMC9779866 DOI: 10.3390/ijms232415492] [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: 10/28/2022] [Revised: 11/24/2022] [Accepted: 12/01/2022] [Indexed: 12/12/2022] Open
Abstract
Pulpal and periapical diseases are the most common dental diseases. The traditional treatment is root canal therapy, which achieves satisfactory therapeutic outcomes-especially for mature permanent teeth. Apexification, pulpotomy, and pulp revascularization are common techniques used for immature permanent teeth to accelerate the development of the root. However, there are obstacles to achieving functional pulp regeneration. Recently, two methods have been proposed based on tissue engineering: stem cell transplantation, and cell homing. One of the goals of functional pulp regeneration is to achieve innervation. Nerves play a vital role in dentin formation, nutrition, sensation, and defense in the pulp. Successful neural regeneration faces tough challenges in both animal studies and clinical trials. Investigation of the regeneration and repair of the nerves in the pulp has become a serious undertaking. In this review, we summarize the current understanding of the key stem cells, signaling molecules, and biomaterials that could promote neural regeneration as part of pulp regeneration. We also discuss the challenges in preclinical or clinical neural regeneration applications to guide deep research in the future.
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17
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Wang G, Wu HL, Liu YP, Yan DQ, Yuan ZL, Chen L, Yang Q, Gao YS, Diao B. Pre-clinical study of human umbilical cord mesenchymal stem cell transplantation for the treatment of traumatic brain injury: safety evaluation from immunogenic and oncogenic perspectives. Neural Regen Res 2022; 17:354-361. [PMID: 34269210 PMCID: PMC8463980 DOI: 10.4103/1673-5374.317985] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Stem cell therapy is a promising strategy for the treatment of traumatic brain injury (TBI). However, animal experiments are needed to evaluate safety; in particular, to examine the immunogenicity and tumorigenicity of human umbilical cord mesenchymal stem cells (huMSCs) before clinical application. In this study, huMSCs were harvested from human amniotic membrane and umbilical cord vascular tissue. A rat model of TBI was established using the controlled cortical impact method. Starting from the third day after injury, the rats were injected with 10 μL of 5 × 106/mL huMSCs by cerebral stereotaxis or with 500 μL of 1 × 106/mL huMSCs via the tail vein for 3 successive days. huMSC transplantation decreased the serum levels of proinflammatory cytokines in rats with TBI and increased the serum levels of anti-inflammatory cytokines, thereby exhibiting good immunoregulatory function. The transplanted huMSCs were distributed in the liver, lung and brain injury sites. No abnormal proliferation or tumorigenesis was found in these organs up to 12 months after transplantation. The transplanted huMSCs negligibly proliferated in vivo, and apoptosis was gradually observed at later stages. These findings suggest that huMSC transplantation for the treatment of traumatic brain injury displays good safety. In addition, huMSCs exhibit good immunoregulatory function, which can help prevent and reduce secondary brain injury caused by the rapid release of inflammatory factors after TBI. This study was approved by the Ethics Committee of Wuhan General Hospital of PLA (approval No. 20160054) on November 1, 2016.
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Affiliation(s)
- Gang Wang
- Basic Medical Laboratory, General Hospital of the Central Theater Command; Hubei Key Laboratory of Central Nervous System Tumor and Intervention, Wuhan, Hubei Province, China
| | - Hua-Ling Wu
- Department of Clinical Laboratory, The Third People's Hospital of Yongzhou, Yongzhou, Hunan Province, China
| | - Yue-Ping Liu
- Basic Medical Laboratory, General Hospital of the Central Theater Command; Hubei Key Laboratory of Central Nervous System Tumor and Intervention, Wuhan, Hubei Province, China
| | - De-Qi Yan
- Department of Neurosurgery, 990th Hospital of Joint Logistic Support Troops of PLA, Zhumadian, Henan Province, China
| | - Zi-Lin Yuan
- Basic Medical Laboratory, General Hospital of the Central Theater Command; Hubei Key Laboratory of Central Nervous System Tumor and Intervention, Wuhan, Hubei Province, China
| | - Li Chen
- Basic Medical Laboratory, General Hospital of the Central Theater Command; Hubei Key Laboratory of Central Nervous System Tumor and Intervention, Wuhan, Hubei Province, China
| | - Qian Yang
- Basic Medical Laboratory, General Hospital of the Central Theater Command; Hubei Key Laboratory of Central Nervous System Tumor and Intervention, Wuhan, Hubei Province, China
| | - Yu-Song Gao
- Department of Neurosurgery, 990th Hospital of Joint Logistic Support Troops of PLA, Zhumadian, Henan Province, China
| | - Bo Diao
- Basic Medical Laboratory, General Hospital of the Central Theater Command; Hubei Key Laboratory of Central Nervous System Tumor and Intervention, Wuhan, Hubei Province, China
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18
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Lu N, Wang X, Shi W, Bian L, Zhang X, Yang G, Tang X, Wang J, Zou Y, Weng Y. Black Phosphorus Nanoparticles Promote Osteogenic Differentiation of EMSCs Through Upregulated TG2 Expression. NANOSCALE RESEARCH LETTERS 2021; 16:154. [PMID: 34637014 PMCID: PMC8511187 DOI: 10.1186/s11671-021-03610-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Accepted: 09/28/2021] [Indexed: 05/05/2023]
Abstract
At bio-safe concentrations, black phosphorus nanoparticles activated TG2, and promote the expression of ECM, which further promoted osteogenic differentiation of EMSCs. From these results, we can conclude that black phosphorus nanoparticles are suitable as biological factors in bone tissue engineering. Black phosphorus nanoparticles (BPs) present excellent biocompatibility and good biodegradability, which have been rigorously studied and proven. However, its utilization in bone tissue engineering fields is still in its infancy. Thus, the main purpose of the present study was to investigate the effects of BPs on osteogenic differentiation of ectodermal mesenchymal stem cell (EMSC) in vitro. Biocompatible BPs with high yield were prepared with a simple and efficient ultrasonication technique. EMSCs were isolated from adult rat nasal respiratory mucosa. Then, we treated EMSCs with BPs at different concentrations in vitro and examined the effect of BPs on osteogenic differentiation of EMSCs. In addition, inhibitor of transglutaminase 2 (TG2) and western blot were used to clarify the mechanism of the promoting effect of BPs on osteogenesis. Our results indicated that BPs could significantly enhance osteogenic differentiation of EMSCs in vitro. Nevertheless, BPs had no effect on EMSCs proliferation. Mechanistically, BPs promoted osteogenesis differentiation of EMSCs through upregulating TG2 expression. These results highlight the advantage of using chemical materials for novel engineering strategies of these highly promising small molecules for bone-tissue regeneration.
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Affiliation(s)
- Naiyan Lu
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, 214122, Jiangsu Province, People's Republic of China
| | - Xinhe Wang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, 214122, Jiangsu Province, People's Republic of China
| | - Wentao Shi
- School of Medicine, Jiangnan University, Wuxi, 214122, Jiangsu Province, People's Republic of China
| | - Lu Bian
- School of Medicine, Jiangnan University, Wuxi, 214122, Jiangsu Province, People's Republic of China
| | - Xuan Zhang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, 214122, Jiangsu Province, People's Republic of China
| | - Guofeng Yang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, 214122, Jiangsu Province, People's Republic of China
| | - Xue Tang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, 214122, Jiangsu Province, People's Republic of China
| | - Jun Wang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, 214122, Jiangsu Province, People's Republic of China
| | - Yin Zou
- The Affiliated Wuxi Children's Hospital of Nanjing Medical University, Wuxi, 214023, Jiangsu Province, People's Republic of China.
| | - Yuyan Weng
- Center for Soft Condensed Matter Physics and Interdisciplinary Research, Soochow University, Suzhou, 215006, People's Republic of China.
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19
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Schweich-Adami LDC, Bernardi L, Baranoski A, Rodrigues TDAF, Antoniolli-Silva ACMB, Oliveira RJ. The enzymatic disaggregation by trypsin does not alter cell quality and genomic stability of adipose-derived stem cells cultivated for human cell therapy. Cell Tissue Bank 2021; 23:641-652. [PMID: 34545505 DOI: 10.1007/s10561-021-09958-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Accepted: 09/03/2021] [Indexed: 11/26/2022]
Abstract
There is no consensus between the protocols used for the isolation, maintenance and cultivation of Adipose-derived stem cells (ADSCs) for therapeutic purposes. Thus, was evaluated the maintenance method of ADSCs submitted to enzymatic disaggregation by trypsin. Was made (1st until 10th passage) immunophenotyping, cell differentiation assays, comet assay, differential cell death, apoptosis, cell viability and membrane integrity by flow cytometry.The results showded that trypsinization,did not induce genomic instability, also did not alter the tail moment. The cell death assay, showed that only on the 10th passage there was a significant reduction and was cofirmed by flow cytometry that is apoptosis. The viability showded significant reduction only in 10th passage, this was related to the loss of integrity of membrane, proven by flow cytometry. The quantities varied along the passages (11 × 105 to 2 × 105). Qualitatively, it can be observed that as the number of cells decreases, there is also a reduction in the juxtaposition of ADSCs and increased of the cell size, it is started in 6th passage. In view of the results, it is suggested for more safety, that ADSCs cultured until the 5th passage being used in human transplantation procedures.
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Affiliation(s)
- Laynna de Carvalho Schweich-Adami
- Stem Cell, Cell Therapy and Toxicological Genetics Research Centre (CeTroGen), "Maria Aparecida Pedrossian" University Hospital, Brazilian Hospital Services Company (EBSERH), Campo Grande, Mato Grosso do Sul, Brazil
- Graduate Program in Health and Development in the Central-West Region, Faculty of Medicine, Federal University of Mato Grosso do Sul (UFMS), Mato Grosso do Sul, MS, Brazil
| | - Luana Bernardi
- Stem Cell, Cell Therapy and Toxicological Genetics Research Centre (CeTroGen), "Maria Aparecida Pedrossian" University Hospital, Brazilian Hospital Services Company (EBSERH), Campo Grande, Mato Grosso do Sul, Brazil
- Graduate Program in Health and Development in the Central-West Region, Faculty of Medicine, Federal University of Mato Grosso do Sul (UFMS), Mato Grosso do Sul, MS, Brazil
| | - Adrivanio Baranoski
- Stem Cell, Cell Therapy and Toxicological Genetics Research Centre (CeTroGen), "Maria Aparecida Pedrossian" University Hospital, Brazilian Hospital Services Company (EBSERH), Campo Grande, Mato Grosso do Sul, Brazil
- Graduate Program in Health and Development in the Central-West Region, Faculty of Medicine, Federal University of Mato Grosso do Sul (UFMS), Mato Grosso do Sul, MS, Brazil
| | - Thais de Andrade Farias Rodrigues
- Stem Cell, Cell Therapy and Toxicological Genetics Research Centre (CeTroGen), "Maria Aparecida Pedrossian" University Hospital, Brazilian Hospital Services Company (EBSERH), Campo Grande, Mato Grosso do Sul, Brazil
| | - Andréia Conceição Milan Brochado Antoniolli-Silva
- Stem Cell, Cell Therapy and Toxicological Genetics Research Centre (CeTroGen), "Maria Aparecida Pedrossian" University Hospital, Brazilian Hospital Services Company (EBSERH), Campo Grande, Mato Grosso do Sul, Brazil
- Graduate Program in Health and Development in the Central-West Region, Faculty of Medicine, Federal University of Mato Grosso do Sul (UFMS), Mato Grosso do Sul, MS, Brazil
| | - Rodrigo Juliano Oliveira
- Stem Cell, Cell Therapy and Toxicological Genetics Research Centre (CeTroGen), "Maria Aparecida Pedrossian" University Hospital, Brazilian Hospital Services Company (EBSERH), Campo Grande, Mato Grosso do Sul, Brazil.
- Graduate Program in Health and Development in the Central-West Region, Faculty of Medicine, Federal University of Mato Grosso do Sul (UFMS), Mato Grosso do Sul, MS, Brazil.
- Graduate Programme in Genetics and Molecular Biology, Department of General Biology, State University of Londrina (UEL), Londrina, Paraná, Brazil.
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Calcat-i-Cervera S, Sanz-Nogués C, O'Brien T. When Origin Matters: Properties of Mesenchymal Stromal Cells From Different Sources for Clinical Translation in Kidney Disease. Front Med (Lausanne) 2021; 8:728496. [PMID: 34616756 PMCID: PMC8488400 DOI: 10.3389/fmed.2021.728496] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Accepted: 08/19/2021] [Indexed: 12/14/2022] Open
Abstract
Advanced therapy medicinal products (ATMPs) offer new prospects to improve the treatment of conditions with unmet medical needs. Kidney diseases are a current major health concern with an increasing global prevalence. Chronic renal failure appears after many years of impairment, which opens a temporary window to apply novel therapeutic approaches to delay or halt disease progression. The immunomodulatory, anti-inflammatory, and pro-regenerative properties of mesenchymal stromal cells (MSCs) have sparked interest for their use in cell-based regenerative therapies. Currently, several early-phase clinical trials have been completed and many are ongoing to explore MSC safety and efficacy in a wide range of nephropathies. However, one of the current roadblocks to the clinical translation of MSC therapies relates to the lack of standardization and harmonization of MSC manufacturing protocols, which currently hinders inter-study comparability. Studies have shown that cell culture processing variables can have significant effects on MSC phenotype and functionality, and these are highly variable across laboratories. In addition, heterogeneity within MSC populations is another obstacle. Furthermore, MSCs may be isolated from several sources which adds another variable to the comparative assessment of outcomes. There is now a growing body of literature highlighting unique and distinctive properties of MSCs according to the tissue origin, and that characteristics such as donor, age, sex and underlying medical conditions may alter the therapeutic effect of MSCs. These variables must be taken into consideration when developing a cell therapy product. Having an optimal scale-up strategy for MSC manufacturing is critical for ensuring product quality while minimizing costs and time of production, as well as avoiding potential risks. Ideally, optimal scale-up strategies must be carefully considered and identified during the early stages of development, as making changes later in the bioprocess workflow will require re-optimization and validation, which may have a significant long-term impact on the cost of the therapy. This article provides a summary of important cell culture processing variables to consider in the scale-up of MSC manufacturing as well as giving a comprehensive review of tissue of origin-specific biological characteristics of MSCs and their use in current clinical trials in a range of renal pathologies.
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Affiliation(s)
| | | | - Timothy O'Brien
- Regenerative Medicine Institute (REMEDI), CÚRAM, Biomedical Science Building, National University of Ireland, Galway, Ireland
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21
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Pain relief and cartilage repair by Nanofat against osteoarthritis: preclinical and clinical evidence. Stem Cell Res Ther 2021; 12:477. [PMID: 34446107 PMCID: PMC8390235 DOI: 10.1186/s13287-021-02538-9] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Accepted: 08/05/2021] [Indexed: 02/08/2023] Open
Abstract
Background Osteoarthritis (OA) is the most common joint degenerative disorder, with little effective therapy to date. Nanofat is a cocktail of cells obtained from fat tissue, which possesses regenerative capacity and has a potential in treating OA. This study aimed to determine the anti-OA efficacy of Nanofat from basic and clinical aspects and explore its action mode. Methods Flow cytometry was performed to characterize Nanofat. A monoiodoacetate-induced OA rat model was employed for in vivo study. Cell viability and wound healing assays were conducted for in vitro study. Real-time PCR and Western blot assays were applied to explore the molecular action mode of Nanofat. Moreover, a retrospective analysis was conducted to determine the clinical efficacy and safety of Nanofat on knee OA patients. Results The in vivo results showed that Nanofat significantly attenuated pain symptoms and protected cartilage ECM (Col2) from damage, and its effects were not significantly differed with adipose tissue-derived stem cells (both P > 0.05). The in vitro results showed that Nanofat promoted the cell viability and migration of chondrocytes and significantly restored the IL-1β-induced abnormal gene expressions of Col2, Aggrecan, Sox9, Adamts5, Mmp3, Mmp9 Mmp13, IL-6 and Col10 and protein expressions of Col2, MMP9, MMP13, and Sox9 of chondrocytes. The regulatory actions of Nanofat on these anabolic, catabolic, and hypertrophic molecules of chondrocytes were similar between two treatment routes: co-culture and conditioned medium, suggesting a paracrine-based mode of action of Nanofat. Moreover, the clinical data showed that Nanofat relieved pain and repaired damaged cartilage of OA patients, with no adverse events. Conclusion In sum, this study demonstrated the anti-OA efficacy as well as a paracrine-based action mode of Nanofat, providing novel knowledge of Nanofat and suggesting it as a promising and practical cell therapy for clinical treatment of OA.
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Yang R, Chen G, Muhashi M, Aizezi G, Jiang M, Yuan H. Adjuvant treatment with adipose-derived mesenchymal stem cells (ADSC) reduces severe refractory hemorrhagic cystitis after RIC-PBSCT: A case report. Medicine (Baltimore) 2021; 100:e26316. [PMID: 34190149 PMCID: PMC8257885 DOI: 10.1097/md.0000000000026316] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Accepted: 05/25/2021] [Indexed: 01/04/2023] Open
Abstract
INTRODUCTION Severe hemorrhagic cystitis (HC) is still a common complication after allogeneic hematopoietic stem cell transplantation, which affects the quality of life of patients, and may even cause kidney failure. This study reports the clinical effect of adjuvant treatment of adipose-derived mesenchymal stem cells (ADSCs) on severe refractory HC after of reduced intensity conditioning haplotype high-dose peripheral blood hematopoietic stem cell transplantation (RIC-PBSCT) in one case. PATIENT CONCERNS A 53-year-old female patient with acute myeloid leukemia (FLT3-ITD) at high risk received RIC-PBSCT. The patient was relieved with complete donor chimerism of 99.01%, and normal hemogram. However, the patient developed frequent urination, urgency, and dysuria with gross hematuria with blood clots and difficult urinating, especially at night and early in the morning. There were obvious hyperemia and bleeding points in the mucosa of the posterior wall of the bladder. DIAGNOSIS The patient was diagnosed as delayed HC of degree IV. INTERVENTIONS AND OUTCOMES The patient was treated with antiviral drugs, urine alkalization, and diuretic drugs for more than 1 month, but no significant effect was obtained. Thus, the patient was then given ADSCs (1 × 106 kg per kg of body weight, infused once a week for a total of 3 infusions). Symptoms of frequent urination, urgency, and dysuria that happened during the first infusion were improved, and blood clots in the urine were also reduced. After the third infusion, HC symptoms disappeared, the red blood cells were normal, and there was no fever, chills, low infusion blood pressure, or rash. The patient's HC was cured. During follow-up, HC recurrence was not observed. CONCLUSION ADSCs adjuvant treatment of relapsed and refractory severe HC is safe and reliable with good clinical efficacy. It shows certain clinical application value, which however requires more clinical cases to further verify this.
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Abstract
PURPOSE OF REVIEW Multiple new medications with novel mechanisms of action are now available to treat Crohn's disease (CD). However, they have varying effectiveness in the management of perianal CD. Identifying the most appropriate therapy and optimizing it is essential to maximize effectiveness of therapy. Additionally, the management of perianal CD requires imaging of the perianal area to identify the fistula anatomy and local complications such as abscesses that require surgical drainage. Initial surgical assessment is key to drain abscesses and allow fistula healing with medical therapy. RECENT FINDINGS Although anti-tumor necrosis factor (TNFs) remain the most effective medications to treat perianal CD, real-world data suggests that ustekinumab may be a 2nd-line option in patients nonresponsive to an anti-TNF or having contraindications. Mesenchymal stem cells are an emerging therapeutic approach that is currently in Phase 3 trials in the United States and poised to play a major role in the treatment algorithm. SUMMARY The management of perianal CD requires a multidisciplinary approach with a combination of initial imaging and surgical assessment to adequately control local sepsis, optimization of biological therapy with adjunct antibiotics or immunomodulators, and close clinical follow-up with imaging to evaluate response to therapy and guide further surgical management options.
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Razeghian-Jahromi I, Matta AG, Canitrot R, Zibaeenezhad MJ, Razmkhah M, Safari A, Nader V, Roncalli J. Surfing the clinical trials of mesenchymal stem cell therapy in ischemic cardiomyopathy. Stem Cell Res Ther 2021; 12:361. [PMID: 34162424 PMCID: PMC8220796 DOI: 10.1186/s13287-021-02443-1] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Accepted: 06/09/2021] [Indexed: 12/15/2022] Open
Abstract
While existing remedies failed to fully address the consequences of heart failure, stem cell therapy has been introduced as a promising approach. The present review is a comprehensive appraisal of the impacts of using mesenchymal stem cells (MSCs) in clinical trials mainly conducted on ischemic cardiomyopathy. The benefits of MSC therapy for dysfunctional myocardium are likely attributed to numerous secreted paracrine factors and immunomodulatory effects. The positive outcomes associated with MSC therapy are scar size reduction, reverse remodeling, and angiogenesis. Also, a decreasing in the level of chronic inflammatory markers of heart failure progression like TNF-α is observed. The intense inflammatory reaction in the injured myocardial micro-environment predicts a poor response of scar tissue to MSC therapy. Subsequently, the interval delay between myocardial injury and MSC therapy is not yet determined. The optimal requested dose of cells ranges between 100 to 150 million cells. Allogenic MSCs have different advantages compared to autogenic cells and intra-myocardial injection is the preferred delivery route. The safety and efficacy of MSCs-based therapy have been confirmed in numerous studies, however several undefined parameters like route of administration, optimal timing, source of stem cells, and necessary dose are limiting the routine use of MSCs therapeutic approach in clinical practice. Lastly, pre-conditioning of MSCs and using of exosomes mediated MSCs or genetically modified MSCs may improve the overall therapeutic effect. Future prospective studies establishing a constant procedure for MSCs transplantation are required in order to apply MSC therapy in our daily clinical practice and subsequently improving the overall prognosis of ischemic heart failure patients.
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Affiliation(s)
| | - Anthony G Matta
- Department of Cardiology, Institute CARDIOMET, University Hospital of Toulouse, Toulouse, France.,Faculty of medicine, Holy Spirit University of Kaslik, Kaslik, Lebanon
| | - Ronan Canitrot
- Department of Cardiology, Institute CARDIOMET, University Hospital of Toulouse, Toulouse, France
| | | | - Mahboobeh Razmkhah
- Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Anahid Safari
- Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Vanessa Nader
- Department of Cardiology, Institute CARDIOMET, University Hospital of Toulouse, Toulouse, France.,Faculty of Pharmacy, Lebanese University, Beirut, Lebanon
| | - Jerome Roncalli
- Department of Cardiology, Institute CARDIOMET, University Hospital of Toulouse, Toulouse, France. .,Service de Cardiologie A, CHU de Toulouse, Hôpital de Rangueil, 1 avenue Jean Poulhès, TSA 50032, 31059, Toulouse Cedex 9, France.
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Nifosì G, Nifosì L, Nifosì AF. Mesenchymal stem cells in the treatment of osteonecrosis of the jaw. J Korean Assoc Oral Maxillofac Surg 2021; 47:65-75. [PMID: 33911038 PMCID: PMC8084742 DOI: 10.5125/jkaoms.2021.47.2.65] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2020] [Revised: 11/08/2020] [Accepted: 11/10/2020] [Indexed: 12/22/2022] Open
Abstract
Medication-related osteonecrosis of the jaw (MRONJ) has recently associated to the increase in antiresorptive and anti-angiogenic drugs prescriptions in the treatment of oncologic and osteoporotic patients. The physiopathogenesis of MRONJ remains unclear and available treatments are unsatisfactory. Newer pharmacological treatments have shown good results, but are not curative and could have major side effects. At the same time as pharmacological treatments, mesenchymal stem cells (MSCs) have emerged as a promising therapeutic modality for tissue regeneration and repair. MSCs are multipotential non-hematopoietic progenitor cells capable to differentiating into multiple lineages of the mesenchyme. Bone marrow MSCs can differentiate into osteogenic cells and display immunological properties and secrete paracrine anti-inflammatory factors in damaged tissues. The immunomodulatory, reparative, and anti-inflammatory properties of bone marrow MSCs have been tested in a variety of animal models of MRONJ and applied in specific clinical settings. The aim of this review is to discuss critically the immunogenicity and immunomodulatory properties of MSCs, both in vitro and in vivo, the possible underlying mechanisms of their effects, and their potential clinical use as modulators of immune responses in MRONJ, and to identify clinical safety and recommendations for future research.
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Jahed FJ, Rahbarghazi R, Shafaei H, Rezabakhsh A, Karimipour M. Application of neurotrophic factor-secreting cells (astrocyte - Like cells) in the in-vitro Alzheimer's disease-like pathology on the human neuroblastoma cells. Brain Res Bull 2021; 172:180-189. [PMID: 33895268 DOI: 10.1016/j.brainresbull.2021.04.014] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Revised: 04/10/2021] [Accepted: 04/19/2021] [Indexed: 10/21/2022]
Abstract
This study investigated physical proximity and paracrine activity of neurotrophic factor-secreting cells (NTF-SCs) on beta-amyloid treated cells. Mesenchymal stem cells (MSCs) - to-NTF-SCs (Astrocyte -like cells) trans-differentiation was confirmed using immunofluorescence staining of GFAP. BDNF and NGF levels were measured by ELISA. To mimic AD-like condition, SH-SY5Y cells were exposed to 10 μM Aβ1-42. SH-SY5Y cells were allocated into Control; and Aβ1-42-treated cells. Treated cells were further classified into three subgroups including Aβ1-42 cells, Aβ1-42 cells + NTF-SCs (CM) and Aβ1-42 cells + NTF-SCs co-culture. Cell viability was measured by MTT assay. Anti-inflammatory and anti-tau hyperphosphorylation effects of NTF-SCs were assessed via monitoring TNF-α and hyperphosphorylated Tau protein expression level respectively. To explore the impact of NTF-SCs on synaptogenesis and synaptic functionality, real-time PCR assay was performed to measure the expression of synapsine 1, homer 1 and ZIF268. The level of synaptophysin was monitored via immunofluorescence staining. Data showed MSCs potential in trans-differentiating toward NTF-SCs indicated with enhanced GFAP expression (p < 0.05). ELISA assay confirmed the superiority of NTF-SCs in releasing NGF and BDNF compared to the MSCs (p < 0.05). Aβ significantly induced SH-SY5Y cells death while juxtacrine and paracrine activity of NTF-SCs significantly blunted these conditions (p < 0.05). Trans-differentiated cells had potential to reduce Tau hyperphosphorylation and TNF-α level after treatment with Aβ through juxtacrine and paracrine mechanisms (p < 0.05). Moreover, NTF-SCs significantly increased the expression rate of synapsin 1, homer 1 and zif 268 genes in Aβ-treated cells compared to matched-control group coincided with induction of synaptophysin at the protein level(p < 0.05). NTF-SCs reversed AD-like neuropathological alterations in SH-SY5Y cells via paracrine and juxtacrine mechanisms.
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Affiliation(s)
- Fatemeh Jafari Jahed
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Reza Rahbarghazi
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hajar Shafaei
- Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Aysa Rezabakhsh
- Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad Karimipour
- Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
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Cao Y, Yan J, Liu H. [Clinical research progress of mesenchymal stem cells in treatment of chronic wounds]. ZHONGGUO XIU FU CHONG JIAN WAI KE ZA ZHI = ZHONGGUO XIUFU CHONGJIAN WAIKE ZAZHI = CHINESE JOURNAL OF REPARATIVE AND RECONSTRUCTIVE SURGERY 2021; 35:496-501. [PMID: 33855836 DOI: 10.7507/1002-1892.202011009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Objective To review the clinical research progress of mesenchymal stem cells (MSCs) in the treatment of chronic wounds. Methods The literature related to the chronic wound repair with MSCs at home and abroad in recent years was extensively reviewed, and the possible mechanism of MSCs in the treatment of chronic wounds, as well as its application and existing problems were summarized. Results MSCs can participate in all aspects of chronic wound healing to promote wound healing, and has shown broad application prospects in clinical trials. MSCs commonly used in clinical research include bone marrow-derived MSCs, adipose-derived tissue MSCs, and umbilical cord-derived MSCs. Conclusion MSCs treatment is a promising strategy for the chronic wounds, but there are still many problems in its widespread clinical application that require further research.
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Affiliation(s)
- Yingxuan Cao
- Department of Plastic Surgery, the First Affiliated Hospital of Jinan University, Innovative Technology Research Institute of Tissue Repair and Regeneration, Key Laboratory of Regenerative Medicine, Ministry of Education, Guangzhou Guangdong, 510630, P.R.China
| | - Jianxin Yan
- Department of Plastic Surgery, the First Affiliated Hospital of Jinan University, Innovative Technology Research Institute of Tissue Repair and Regeneration, Key Laboratory of Regenerative Medicine, Ministry of Education, Guangzhou Guangdong, 510630, P.R.China
| | - Hongwei Liu
- Department of Plastic Surgery, the First Affiliated Hospital of Jinan University, Innovative Technology Research Institute of Tissue Repair and Regeneration, Key Laboratory of Regenerative Medicine, Ministry of Education, Guangzhou Guangdong, 510630, P.R.China
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MicroRNA124 and microRNA21-5p regulate migration, proliferation and differentiation of rat bone marrow mesenchymal stem cells. Biosci Rep 2021; 40:226597. [PMID: 33026076 PMCID: PMC7584812 DOI: 10.1042/bsr20193531] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2019] [Revised: 08/29/2020] [Accepted: 10/02/2020] [Indexed: 12/28/2022] Open
Abstract
Mesenchymal stem cells (MSCs) are multipotent stromal cells that can be a useful source of cells for the treatment of many diseases, including neurologic diseases. The curative effect of MSCs relies mostly on cell’s capacity of migration, proliferation and differentiation. MicroRNAs (miRNAs) are small non-coding RNAs that play important roles on regulating various cell behaviors. Here, we report that miRNA-124 (miR124) and miRNA-21-5p (miR21-5p) display different regulatory roles on migration, proliferation and neuron differentiation of MSCs. MiR124 was shown greatly promoting MSCs migration and neuronal differentiation. MiR21-5p could significantly enhance the proliferation and neuronal differentiation ability of MSCs. MiR124 and miR21-5p synergistically promote differentiation of MSCs into neurons. Collectively, miR124 and miR21-5p can functionally regulate cell migration, proliferation and neuronal differentiation of MSCs. Therefore, miR124 and miR21-5p may be promising tools to improve transplantation efficiency for neural injury.
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Aprile D, Alessio N, Demirsoy IH, Squillaro T, Peluso G, Di Bernardo G, Galderisi U. MUSE Stem Cells Can Be Isolated from Stromal Compartment of Mouse Bone Marrow, Adipose Tissue, and Ear Connective Tissue: A Comparative Study of Their In Vitro Properties. Cells 2021; 10:761. [PMID: 33808472 PMCID: PMC8065981 DOI: 10.3390/cells10040761] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Revised: 03/25/2021] [Accepted: 03/29/2021] [Indexed: 01/10/2023] Open
Abstract
The cells present in the stromal compartment of many tissues are a heterogeneous population containing stem cells, progenitor cells, fibroblasts, and other stromal cells. A SSEA3(+) cell subpopulation isolated from human stromal compartments showed stem cell properties. These cells, known as multilineage-differentiating stress-enduring (MUSE) cells, are capable of resisting stress and possess an excellent ability to repair DNA damage. We isolated MUSE cells from different mouse stromal compartments, such as those present in bone marrow, subcutaneous white adipose tissue, and ear connective tissue. These cells showed overlapping in vitro biological properties. The mouse MUSE cells were positive for stemness markers such as SOX2, OCT3/4, and NANOG. They also expressed TERT, the catalytic telomerase subunit. The mouse MUSE cells showed spontaneous commitment to differentiation in meso/ecto/endodermal derivatives. The demonstration that multilineage stem cells can be isolated from an animal model, such as the mouse, could offer a valid alternative to the use of other stem cells for disease studies and envisage of cellular therapies.
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Affiliation(s)
- Domenico Aprile
- Department of Experimental Medicine, Luigi Vanvitelli Campania University, 80138 Naples, Italy; (D.A.); (N.A.); (I.H.D.); (T.S.); (G.D.B.)
| | - Nicola Alessio
- Department of Experimental Medicine, Luigi Vanvitelli Campania University, 80138 Naples, Italy; (D.A.); (N.A.); (I.H.D.); (T.S.); (G.D.B.)
| | - Ibrahim H. Demirsoy
- Department of Experimental Medicine, Luigi Vanvitelli Campania University, 80138 Naples, Italy; (D.A.); (N.A.); (I.H.D.); (T.S.); (G.D.B.)
| | - Tiziana Squillaro
- Department of Experimental Medicine, Luigi Vanvitelli Campania University, 80138 Naples, Italy; (D.A.); (N.A.); (I.H.D.); (T.S.); (G.D.B.)
| | | | - Giovanni Di Bernardo
- Department of Experimental Medicine, Luigi Vanvitelli Campania University, 80138 Naples, Italy; (D.A.); (N.A.); (I.H.D.); (T.S.); (G.D.B.)
- Center for Biotechnology, Sbarro Institute for Cancer Research and Molecular Medicine, Temple University, Philadelphia, PA 19122, USA
| | - Umberto Galderisi
- Department of Experimental Medicine, Luigi Vanvitelli Campania University, 80138 Naples, Italy; (D.A.); (N.A.); (I.H.D.); (T.S.); (G.D.B.)
- Center for Biotechnology, Sbarro Institute for Cancer Research and Molecular Medicine, Temple University, Philadelphia, PA 19122, USA
- Genome and Stem Cell Center (GENKOK), Erciyes University, 38280 Kayseri, Turkey
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Jin M, Kim BS, Seo SH, Kim M, Kang YG, Shin JW, Cho KH, Shin MC, Yoon C, Min KA. Synergistic Effect of Growth Factor Releasing Polymeric Nanoparticles and Ultrasound Stimulation on Osteogenic Differentiation. Pharmaceutics 2021; 13:pharmaceutics13040457. [PMID: 33801692 PMCID: PMC8066944 DOI: 10.3390/pharmaceutics13040457] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 03/24/2021] [Accepted: 03/25/2021] [Indexed: 01/16/2023] Open
Abstract
Mesenchymal stem cells (MSCs) have been extensively used in the tissue regeneration therapy. Ex vivo therapy with well-differentiated osteogenic cells is known as an efficient treatment for musculoskeletal diseases, including rheumatoid diseases. However, along with its high cost, the current therapy has limitations in terms of restoring bone regeneration procedures. An efficient process for the cell differentiation to obtain a large number of functionalized osteogenic cells is necessary. Therefore, it is strongly recommended to develop strategies to produce sufficient numbers of well-differentiated osteogenic cells from the MSCs. In general, differentiation media with growth factors have been used to facilitate cell differentiation. In the present study, the poly (lactic-co-glycolic acid) (PLGA) nanoparticles incorporating the growth factors were included in the media, resulting in releasing growth factors (dexamethasone and β-glycerophosphate) in the media in the controlled manner. Stable growth and early differentiation of osteogenic cells were achieved by the PLGA-based growth factor releasing system. Moreover, low intensity pulsed ultrasound was applied to this system to induce cell differentiation process. The results revealed that, as a biomarker at early stage of osteogenic cell differentiation, Lamin A/C nuclear protein was efficiently expressed in the cells growing in the presence of PLGA-based growth factor reservoirs and ultrasound. In conclusion, our results showed that the ultrasound stimulation combined with polymeric nanoparticles releasing growth factors could potentially induce osteogenic cell differentiation.
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Affiliation(s)
- Minki Jin
- College of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research, Inje University, 197 Injero, Gimhae 50834, Gyeongnam, Korea; (M.J.); (K.H.C.)
- College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, Korea
| | - Bo Seok Kim
- Department of Nanoscience and Engineering, School of Biomedical Engineering, Inje University, 197 Injero, Gimhae 50834, Gyeongnam, Korea; (B.S.K.); (S.H.S.)
| | - Sung Ho Seo
- Department of Nanoscience and Engineering, School of Biomedical Engineering, Inje University, 197 Injero, Gimhae 50834, Gyeongnam, Korea; (B.S.K.); (S.H.S.)
| | - Minjeong Kim
- Department of Biomedical Engineering, Inje University, 197 Injero, Gimhae 50834, Gyeongnam, Korea; (M.K.); (Y.G.K.); (J.-W.S.)
| | - Yun Gyeong Kang
- Department of Biomedical Engineering, Inje University, 197 Injero, Gimhae 50834, Gyeongnam, Korea; (M.K.); (Y.G.K.); (J.-W.S.)
| | - Jung-Woog Shin
- Department of Biomedical Engineering, Inje University, 197 Injero, Gimhae 50834, Gyeongnam, Korea; (M.K.); (Y.G.K.); (J.-W.S.)
| | - Kwan Hyung Cho
- College of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research, Inje University, 197 Injero, Gimhae 50834, Gyeongnam, Korea; (M.J.); (K.H.C.)
| | - Meong Cheol Shin
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, 501 Jinju Daero, Jinju 52828, Gyeongnam, Korea;
| | - Changhan Yoon
- Department of Nanoscience and Engineering, School of Biomedical Engineering, Inje University, 197 Injero, Gimhae 50834, Gyeongnam, Korea; (B.S.K.); (S.H.S.)
- Department of Biomedical Engineering, Inje University, 197 Injero, Gimhae 50834, Gyeongnam, Korea; (M.K.); (Y.G.K.); (J.-W.S.)
- Correspondence: (C.Y.); (K.A.M.); Tel.: +82-55-320-3301 (C.Y.); +82-55-320-3459 (K.A.M.)
| | - Kyoung Ah Min
- College of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research, Inje University, 197 Injero, Gimhae 50834, Gyeongnam, Korea; (M.J.); (K.H.C.)
- Correspondence: (C.Y.); (K.A.M.); Tel.: +82-55-320-3301 (C.Y.); +82-55-320-3459 (K.A.M.)
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Casati S, Giannasi C, Niada S, Bergamaschi RF, Orioli M, Brini AT. Bioactive Lipids in MSCs Biology: State of the Art and Role in Inflammation. Int J Mol Sci 2021; 22:1481. [PMID: 33540695 PMCID: PMC7867257 DOI: 10.3390/ijms22031481] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Revised: 01/28/2021] [Accepted: 01/29/2021] [Indexed: 12/11/2022] Open
Abstract
Lipidomics is a lipid-targeted metabolomics approach that aims to the comprehensive analysis of lipids in biological systems in order to highlight the specific functions of lipid species in health and disease. Lipids play pivotal roles as they are major structural components of the cellular membranes and energy storage molecules but also, as most recently shown, they act as functional and regulatory components of intra- and intercellular signaling. Herein, emphasis is given to the recently highlighted roles of specific bioactive lipids species, as polyunsaturated fatty acids (PUFA)-derived mediators (generally known as eicosanoids), endocannabinoids (eCBs), and lysophospholipids (LPLs), and their involvement in the mesenchymal stem cells (MSCs)-related inflammatory scenario. Indeed, MSCs are a heterogenous population of multipotent cells that have attracted much attention for their potential in regulating inflammation, immunomodulatory capabilities, and reparative roles. The lipidomics of the inflammatory disease osteoarthritis (OA) and the influence of MSCs-derived lipids have also been addressed.
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Affiliation(s)
- Sara Casati
- Dipartimento di Scienze Biomediche, Chirurgiche ed Odontoiatriche, Università degli Studi di Milano, 20133 Milan, Italy; (C.G.); (R.F.B.); (M.O.); (A.T.B.)
| | - Chiara Giannasi
- Dipartimento di Scienze Biomediche, Chirurgiche ed Odontoiatriche, Università degli Studi di Milano, 20133 Milan, Italy; (C.G.); (R.F.B.); (M.O.); (A.T.B.)
- IRCCS Istituto Ortopedico Galeazzi, 20161 Milan, Italy;
| | | | - Roberta F. Bergamaschi
- Dipartimento di Scienze Biomediche, Chirurgiche ed Odontoiatriche, Università degli Studi di Milano, 20133 Milan, Italy; (C.G.); (R.F.B.); (M.O.); (A.T.B.)
| | - Marica Orioli
- Dipartimento di Scienze Biomediche, Chirurgiche ed Odontoiatriche, Università degli Studi di Milano, 20133 Milan, Italy; (C.G.); (R.F.B.); (M.O.); (A.T.B.)
| | - Anna T. Brini
- Dipartimento di Scienze Biomediche, Chirurgiche ed Odontoiatriche, Università degli Studi di Milano, 20133 Milan, Italy; (C.G.); (R.F.B.); (M.O.); (A.T.B.)
- IRCCS Istituto Ortopedico Galeazzi, 20161 Milan, Italy;
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Akita N, Narita Y, Yamawaki-Ogata A, Usui A, Komori K. Therapeutic effect of allogeneic bone marrow-derived mesenchymal stromal cells on aortic aneurysms. Cell Tissue Res 2021; 383:781-793. [PMID: 33146827 DOI: 10.1007/s00441-020-03295-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2019] [Accepted: 09/14/2020] [Indexed: 01/14/2023]
Abstract
We previously reported the effectiveness of autologous mesenchymal stromal cells (MSCs) for the treatment of aortic aneurysm (AA), mediated mainly by these cells' anti-inflammatory properties. In this study, we investigate whether the therapeutic effects of allogeneic MSCs on AA are the same as those of autologous MSCs. To examine the immune response to allogeneic MSCs, C57BL/6 lymphocytes were co-cultured with BALB/c MSCs for 5 days in vitro. Apolipoprotein E-deficient C57BL/6 mice with AA induced by angiotensin II were randomly divided into three groups defined by the following intravenous injections: (i) 0.2 ml of saline (n = 10, group S) as a control, (ii) 1 × 106 autologous MSCs (isolated from C57BL/6, n = 10, group Au) and (iii) 1 × 106 allogeneic MSCs (isolated from BALB/c, n = 10, group Al). Two weeks after injection, aortic diameters were measured, along with enzymatic activities of MMP-2 and MMP-9 and cytokine concentrations in AAs. Neither allogenic (BALB/c) MSCs nor autologous (C57BL/6) MSCs accelerated the proliferation of lymphocytes obtained from C57BL/6. Compared with group S, groups Au and Al had significantly shorter aortic diameters (group S vs Au vs Al; 2.29 vs 1.40 vs 1.36 mm, respectively, p < 0.01), reduced MMP-2 and MMP-9 activities, downregulated IL-6 and MCP-1 and upregulated expression of IGF-1 and TIMP-2. There were no differences in these results between groups Au and Al. Thus, our study suggests that treatment with allogeneic MSCs improves chronic inflammation and reduced aortic dilatation. These effects were equivalent to those of autologous MSCs in established mouse models of AA.
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Affiliation(s)
- Naohiro Akita
- Division of Vascular Surgery, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yuji Narita
- Department of Cardiac Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
| | - Aika Yamawaki-Ogata
- Department of Cardiac Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan
| | - Akihiko Usui
- Department of Cardiac Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan
| | - Kimihiro Komori
- Division of Vascular Surgery, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
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Bami M, Sarlikiotis T, Milonaki M, Vikentiou M, Konsta E, Kapsimali V, Pappa V, Koulalis D, Johnson EO, Soucacos PN. Superiority of synovial membrane mesenchymal stem cells in chondrogenesis, osteogenesis, myogenesis and tenogenesis in a rabbit model. Injury 2020; 51:2855-2865. [PMID: 32201117 DOI: 10.1016/j.injury.2020.03.022] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2020] [Revised: 03/06/2020] [Accepted: 03/07/2020] [Indexed: 02/02/2023]
Abstract
Engineering complex tissues is perhaps the most ambitious goal of all tissue engineers. Despite significant advances in tissue engineering, which have resulted in successful engineering of simple tissues such as skin and cartilage, there are a number of challenges that remain in engineering of complex, hybrid tissue structures, such as osteochondral tissue. Mesenchymal stem cells (MSCs) have the capacity to highly proliferate in an undifferentiated state and the potential to differentiate into a variety of different lineages, providing a promising single cell source to produce multiple cell types. MSC obtained from adult human contribute to the regeneration of mesenchymal tissues such as bone, cartilage, fat, muscle, tendon and marrow stroma. In the present study, the regeneration capacity of multipotent MSCs derived from different tissues in the rabbit were compared. Specifically the aim of this study was to isolate and characterize rabbit adult stem cell populations from bone marrow, adipose, synovial membrane, rotator cuff, ligament and tendon and assess their cell morphology, growth rate, cell surface markers and differentiation capacity. MSCs derived from synovial membrane showed superiority in terms of chondrogenesis, osteogenesis, myogenesis and tenogenesis, suggesting that synovial membrane-derived MSCs would be a good candidate for efforts to regenerate musculoskeletal tissues.
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Affiliation(s)
- Myrto Bami
- Panayotis N. Soucacos", Orthopaedic Research & Education Center (OREC), 1 Rimini Street, Attikon University Hospital, Haidari 124 62 Athens, Greece.
| | - Thomas Sarlikiotis
- Panayotis N. Soucacos", Orthopaedic Research & Education Center (OREC), 1 Rimini Street, Attikon University Hospital, Haidari 124 62 Athens, Greece
| | - Mandy Milonaki
- Panayotis N. Soucacos", Orthopaedic Research & Education Center (OREC), 1 Rimini Street, Attikon University Hospital, Haidari 124 62 Athens, Greece
| | - Myrofora Vikentiou
- Second Department of Internal Medicine and Research Institute, Attikon University General Hospital, 1Rimini Str, Haidari, Athens, Greece
| | - Evgenia Konsta
- Second Department of Internal Medicine and Research Institute, Attikon University General Hospital, 1Rimini Str, Haidari, Athens, Greece
| | - Violetta Kapsimali
- Microbiology Laboratory, Medical School of National and Kapodistrian University of Athens, Athens, Greece
| | - Vasiliki Pappa
- Second Department of Internal Medicine and Research Institute, Attikon University General Hospital, 1Rimini Str, Haidari, Athens, Greece
| | - Dimitrios Koulalis
- Panayotis N. Soucacos", Orthopaedic Research & Education Center (OREC), 1 Rimini Street, Attikon University Hospital, Haidari 124 62 Athens, Greece
| | | | - Panayotis N Soucacos
- Panayotis N. Soucacos", Orthopaedic Research & Education Center (OREC), 1 Rimini Street, Attikon University Hospital, Haidari 124 62 Athens, Greece
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Jordan TL, Maar K, Redhage KR, Misra P, Blancas-Mejia LM, Dick CJ, Wall JS, Williams A, Dietz AB, van Wijnen AJ, Lin Y, Ramirez-Alvarado M. Light chain amyloidosis induced inflammatory changes in cardiomyocytes and adipose-derived mesenchymal stromal cells. Leukemia 2020; 34:1383-1393. [PMID: 31796914 PMCID: PMC7196017 DOI: 10.1038/s41375-019-0640-4] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2019] [Revised: 10/01/2019] [Accepted: 11/04/2019] [Indexed: 01/23/2023]
Abstract
Light chain (AL) amyloidosis is a progressive, degenerative disease characterized by the misfolding and amyloid deposition of immunoglobulin light chain (LC). The amyloid deposits lead to organ failure and death. Our laboratory is specifically interested in cardiac involvement of AL amyloidosis. We have previously shown that the fibrillar aggregates of LC proteins can be cytotoxic and arrest the growth of human RFP-AC16 cardiomyocytes in vitro. We showed that adipose-derived mesenchymal stromal cells (AMSC) can rescue the cardiomyocytes from the fibril-induced growth arrest through contact-dependent mechanisms. In this study, we examined the transcriptome changes of human cardiomyocytes and AMSC in the presence of AL amyloid fibrils. The presence of fibrils causes a 'priming' immune response in AMSC associated with interferon associated genes. Exposure to AL fibrils induced changes in the pathways associated with immune response and extracellular matrix components in cardiomyocytes. We also observed upregulation of innate immune-associated transcripts (chemokines, cytokines, and complement), suggesting that amyloid fibrils initiate an innate immune response on these cells, possibly due to phenotypic transformation. This study corroborates and expands our previous studies and identifies potential new immunologic mechanisms of action for fibril toxicity on human cardiomyocytes and AMSC rescue effect on cardiomyocytes.
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Affiliation(s)
- Torri L Jordan
- Department of Immunology, Mayo Clinic, Rochester, MN, USA
- Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA
| | - Khansaa Maar
- Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA
| | - Keely R Redhage
- Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA
| | - Pinaki Misra
- Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA
| | - Luis M Blancas-Mejia
- Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA
| | - Christopher J Dick
- Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA
| | - Jonathan S Wall
- Departments of Medicine and Radiology, the University of Tennessee Graduate School of Medicine, Knoxville, TN, USA
| | - Angela Williams
- Departments of Medicine and Radiology, the University of Tennessee Graduate School of Medicine, Knoxville, TN, USA
| | - Allan B Dietz
- Immune Progenitor Adoptive Cell Therapy (IMPACT) Lab, Division of Transfusion Medicine, Mayo Clinic, Rochester, MN, USA
| | - Andre J van Wijnen
- Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA
- Center for Regenerative Medicine, Mayo Clinic, Rochester, MN, USA
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
| | - Yi Lin
- Immune Progenitor Adoptive Cell Therapy (IMPACT) Lab, Division of Transfusion Medicine, Mayo Clinic, Rochester, MN, USA.
- Division of Hematology, Mayo Clinic, Rochester, MN, USA.
| | - Marina Ramirez-Alvarado
- Department of Immunology, Mayo Clinic, Rochester, MN, USA.
- Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA.
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Zhao R, Zhang Q, Liu K, Yang P, Sun Y, Zhang Y, Liu Z. Isolation, culture, and induced multiple differentiation of Mongolian sheep adipose-derived mesenchymal stem cells. J Histotechnol 2020; 43:125-134. [PMID: 32314671 DOI: 10.1080/01478885.2020.1744316] [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] [Indexed: 10/24/2022]
Abstract
Adipose-derived mesenchymal stem cells (ADSC) are adult pluripotent cells and important resources for cell-based therapies of animals. There are presently different kinds of somatic cells used as donor cells for clone successfully. However, studies on somatic cell nuclear transplantation (SCNT) using ADSC as donor cells from Mongolian sheep have not been reported up to now. This study tested optimal methods of isolating, purifying, and proliferating Mongolian sheep ADSC, and determine their multiple differentiation potentiality. Adipose tissue was removed from approximately 2-year-old sheep and ADSC were harvested by pancreatic enzyme decomposition and adherent culture method. The growth curves of the Passages 1, 5, and 10 cultures were plotted and the exponential growth was determined as a population doubling time of 34.1 h. The expression of OCT4, SOX2, and NANOG genes were increased at Passage 3 (P3) as seen by reverse transcription polymerase chain reaction (RT-PCR) analysis. ADSC from Passage 3 were induced to undergo neurogenesis and form cardiomyocytes and pancreatic islet-like cells under inductive environments in vitro. The differentiation properties of cardiomyocytes and islet-like cells were confirmed by histological staining with toluidine blue, periodic acid-Schiff, and dithizone. The expression of specific genes in these cells were also detected by RT-PCR. Our study results confirm that isolated cells were indeed ADSC and may provide valuable materials for somatic cell clone and transgenic research.
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Affiliation(s)
- Ruiyuan Zhao
- College of Life Sciences, Inner Mongolia Agricultural University , Hohhot, China.,Department of Biotechnology, Ordos Vocational College of Ecological Environment , Ordos, China
| | - Qian Zhang
- Breeding Research Lab, Animal Husbandry and Veterinary Research Institute of Qingdao , Qingdao, China
| | - Kaidong Liu
- Breeding Research Lab, Animal Husbandry and Veterinary Research Institute of Qingdao , Qingdao, China
| | - Peipei Yang
- Breeding Research Lab, Animal Husbandry and Veterinary Research Institute of Qingdao , Qingdao, China
| | - Youde Sun
- Breeding Research Lab, Animal Husbandry and Veterinary Research Institute of Qingdao , Qingdao, China
| | - Yanru Zhang
- College of Life Sciences, Inner Mongolia Agricultural University , Hohhot, China
| | - Zongzheng Liu
- Breeding Research Lab, Animal Husbandry and Veterinary Research Institute of Qingdao , Qingdao, China
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Conley SM, Hickson LJ, Kellogg TA, McKenzie T, Heimbach JK, Taner T, Tang H, Jordan KL, Saadiq IM, Woollard JR, Isik B, Afarideh M, Tchkonia T, Kirkland JL, Lerman LO. Human Obesity Induces Dysfunction and Early Senescence in Adipose Tissue-Derived Mesenchymal Stromal/Stem Cells. Front Cell Dev Biol 2020; 8:197. [PMID: 32274385 PMCID: PMC7113401 DOI: 10.3389/fcell.2020.00197] [Citation(s) in RCA: 70] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2020] [Accepted: 03/09/2020] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Chronic inflammatory conditions like obesity may adversely impact the biological functions underlying the regenerative potential of mesenchymal stromal/stem cells (MSC). Obesity can impair MSC function by inducing cellular senescence, a growth-arrest program that transitions cells to a pro-inflammatory state. However, the effect of obesity on adipose tissue-derived MSC in human subjects remains unclear. We tested the hypothesis that obesity induces senescence and dysfunction in human MSC. METHODS MSC were harvested from abdominal subcutaneous fat collected from obese and age-matched non-obese subjects (n = 40) during bariatric or kidney donation surgeries, respectively. MSC were characterized, their migration and proliferation assessed, and cellular senescence evaluated by gene expression of cell-cycle arrest and senescence-associated secretory phenotype markers. In vitro studies tested MSC effect on injured human umbilical vein endothelial cells (HUVEC) function. RESULTS Mean age was 59 ± 8 years, 66% were females. Obese subjects had higher body-mass index (BMI) than non-obese. MSC from obese subjects exhibited lower proliferative capacities than non-obese-MSC, suggesting decreased function, whereas their migration remained unchanged. Senescent cell burden and phenotype, manifested as p16, p53, IL-6, and MCP-1 gene expression, were significantly upregulated in obese subjects' MSC. BMI correlated directly with expression of p16, p21, and IL-6. Furthermore, co-incubation with non-obese, but not with obese-MSC, restored VEGF expression and tube formation that were blunted in injured HUVEC. CONCLUSION Human obesity triggers an early senescence program in adipose tissue-derived MSC. Thus, obesity-induced cellular injury may alter efficacy of this endogenous repair system and hamper the feasibility of autologous transplantation in obese individuals.
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Affiliation(s)
- Sabena M. Conley
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, MN, United States
| | - LaTonya J. Hickson
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, MN, United States
- Division of Geriatric Medicine and Gerontology, Department of Medicine, Mayo Clinic, Rochester, MN, United States
| | - Todd A. Kellogg
- Department of Surgery, Mayo Clinic, Rochester, MN, United States
| | - Travis McKenzie
- Department of Surgery, Mayo Clinic, Rochester, MN, United States
| | | | - Timucin Taner
- Division of Geriatric Medicine and Gerontology, Department of Medicine, Mayo Clinic, Rochester, MN, United States
- Department of Immunology, Mayo Clinic, Rochester, MN, United States
| | - Hui Tang
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, MN, United States
| | - Kyra L. Jordan
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, MN, United States
| | - Ishran M. Saadiq
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, MN, United States
| | - John R. Woollard
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, MN, United States
| | - Busra Isik
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, MN, United States
| | - Mohsen Afarideh
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, MN, United States
| | - Tamar Tchkonia
- Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, United States
| | - James L. Kirkland
- Division of Geriatric Medicine and Gerontology, Department of Medicine, Mayo Clinic, Rochester, MN, United States
- Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, United States
| | - Lilach O. Lerman
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, MN, United States
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Adolfsson E, Helenius G, Friberg Ö, Samano N, Frøbert O, Johansson K. Bone marrow- and adipose tissue-derived mesenchymal stem cells from donors with coronary artery disease; growth, yield, gene expression and the effect of oxygen concentration. Scandinavian Journal of Clinical and Laboratory Investigation 2020; 80:318-326. [PMID: 32189529 DOI: 10.1080/00365513.2020.1741023] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Mesenchymal stem cells (MSCs) for cardiovascular cell therapy are procured from different sources including bone marrow and adipose tissue. Differently located MSCs differ in growth potential, differentiation ability and gene expression when cultured in vitro, and studies show different healing abilities for different MSC subgroups. In this study, bone marrow derived MSCs (BMSCs) and adipose tissue derived MSCs (ADSCs) from six human donors with coronary artery disease were compared for growth potential and expression of target genes (Angpt1, LIF, HGF, TGF-β1 and VEGF-A) in response to exposure to 1% and 5% O2, for up to 48 h. We found greater growth of ADSCs compared to BMSCs. ADSCs expressed higher levels of Angpt1, LIF and TGF-β1 and equal levels of VEGF-A and HGF as BMSCs. In BMSCs, exposure to low oxygen resulted in upregulation of TGF-β1, whereas other target genes were unaffected. Upregulation was only present at 1% O2. In ADSCs, LIF was upregulated in both oxygen concentrations, whereas Angpt1 was upregulated only at 1% O2. Different response to reduced oxygen culture conditions is of relevance when expanding cells in vitro prior to administration. These findings indicate ADSCs as better suited for cardiovascular cell therapy compared to BMSCs.
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Affiliation(s)
- Emma Adolfsson
- Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Gisela Helenius
- Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Örjan Friberg
- Department of Cardiothoracic Surgery, Faculty of Health, Örebro University, Örebro, Sweden
| | - Ninos Samano
- Department of Cardiothoracic Surgery, Faculty of Health, Örebro University, Örebro, Sweden
| | - Ole Frøbert
- Department of Cardiology, Faculty of Health, Örebro University, Örebro, Sweden
| | - Karin Johansson
- Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
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Lee HJ, Kim WY. Mesenchymal stromal cell application as an emerging translational medicine for acute respiratory distress syndrome. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:267. [PMID: 32355711 PMCID: PMC7186657 DOI: 10.21037/atm.2020.02.82] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
- Hyun Jung Lee
- Department of Anatomy and Cell Biology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea
| | - Won-Young Kim
- Department of Internal Medicine, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea
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Ceccariglia S, Cargnoni A, Silini AR, Parolini O. Autophagy: a potential key contributor to the therapeutic action of mesenchymal stem cells. Autophagy 2020; 16:28-37. [PMID: 31185790 PMCID: PMC6984485 DOI: 10.1080/15548627.2019.1630223] [Citation(s) in RCA: 94] [Impact Index Per Article: 18.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2018] [Revised: 06/04/2019] [Accepted: 06/04/2019] [Indexed: 12/19/2022] Open
Abstract
Macroautophagy/autophagy occurs at basal levels in all eukaryotic cells and plays an important role in maintaining bio-energetic homeostasis through the control of molecule degradation and organelle turnover. It can be induced by environmental conditions such as starvation, and is deregulated in many diseases including autoimmune diseases, neurodegenerative disorders, and cancer. Interestingly, the modulation of autophagy in mesenchymal stem cells (MSCs) represents a possible mechanism which, affecting MSC properties, may have an impact on their regenerative, therapeutic potential. Furthermore, the ability of MSCs to modulate autophagy of cells in injured tissues/organs has been recently proposed to be involved in the regeneration of damaged tissues and organs. In particular, MSCs can affect autophagy in immune cells involved in injury-induced inflammation reducing their survival, proliferation, and function and favoring the resolution of inflammation. In addition, MSCs can affect autophagy in endogenous adult or progenitor cells, promoting their survival, proliferation and differentiation supporting the restoration of functional tissue. This review provides, for the first time, an overview of the studies which highlight a possible link between the therapeutic properties of MSCs and their ability to modulate autophagy, and it summarizes examples of disorders where these therapeutic properties have been correlated with such modulation. A better elucidation of the mechanism(s) through which MSCs can modulate the autophagy of target cells and how autophagy can affect MSCs therapeutic properties, can provide a wider perspective for the clinical application of MSCs in the treatment of many diseases.Abbreviations: 3-MA: 3-methyladenine; AD: Alzheimer disease; ATG: autophagy-related; BECN1: beclin 1; BM: bone marrow; CD: cluster of differentiation; EAE: experimental autoimmune encephalomyelitis; IL: interleukin; INF: interferon; LAP: LC3-associated phagocytosis; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MSCs: mesenchymal stem cells; MTOR: mechanistic target of rapamycin kinase; PD: Parkinson disease; PtdIns3K: class III phosphatidylinositol 3-kinase; ROS: reactive oxygen species; SLE: systemic lupus erythematosus; SQSTM1: sequestosome 1; TBI: traumatic brain injury; TGF: transforming growth factor; TNF: tumor necrosis factor.
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Affiliation(s)
- Sabrina Ceccariglia
- Istituto di Anatomia Umana e Biologia Cellulare, Università Cattolica del Sacro Cuore, Roma, Italia
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italia
| | - Anna Cargnoni
- Centro di Ricerca “E. Menni”, Fondazione Poliambulanza - Istituto Ospedaliero, Brescia, Italy
| | - Antonietta Rosa Silini
- Centro di Ricerca “E. Menni”, Fondazione Poliambulanza - Istituto Ospedaliero, Brescia, Italy
| | - Ornella Parolini
- Istituto di Anatomia Umana e Biologia Cellulare, Università Cattolica del Sacro Cuore, Roma, Italia
- Centro di Ricerca “E. Menni”, Fondazione Poliambulanza - Istituto Ospedaliero, Brescia, Italy
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Colony Formation, Migratory, and Differentiation Characteristics of Multipotential Stromal Cells (MSCs) from "Clinically Accessible" Human Periosteum Compared to Donor-Matched Bone Marrow MSCs. Stem Cells Int 2019; 2019:6074245. [PMID: 31871468 PMCID: PMC6906873 DOI: 10.1155/2019/6074245] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2019] [Accepted: 11/01/2019] [Indexed: 02/06/2023] Open
Abstract
Periosteum is vital for fracture healing, as a highly vascular and multipotential stromal cell- (MSC-) rich tissue. During surgical bone reconstruction, small fragments of periosteum can be “clinically accessible,” yet periosteum is currently not ultilised, unlike autologous bone marrow (BM) aspirate. This study is aimed at comparing human periosteum and donor-matched iliac crest BM MSC content and characterising MSCs in terms of colony formation, growth kinetics, phenotype, cell migration patterns, and trilineage differentiation capacity. “Clinically accessible” periosteum had an intact outer fibrous layer, containing CD271+ candidate MSCs located perivasculary; the inner cambium was rarely present. Following enzymatic release of cells, periosteum formed significantly smaller fibroblastic colonies compared to BM (6.1 mm2 vs. 15.5 mm2, n = 4, P = 0.0006). Periosteal colonies were more homogenous in size (range 2-30 mm2 vs. 2-54 mm2) and on average 2500-fold more frequent (2.0% vs. 0.0008%, n = 10, P = 0.004) relative to total viable cells. When expanded in vitro, similar growth rates up to passage 0 (P0) were seen (1.8 population doublings (PDs) per day (periosteum), 1.6 PDs per day (BM)); however, subsequently BM MSCs proliferated significantly slower by P4 (4.3 PDs per day (periosteum) vs. 9.3 PDs per day (BM), n = 9, P = 0.02). In early culture, periosteum cells were less migratory at slower speeds than BM cells. Both MSC types exhibited MSC phenotype and trilineage differentiation capacity; however, periosteum MSCs showed significantly lower (2.7-fold) adipogenic potential based on Nile red : DAPI ratios with reduced expression of adipogenesis-related transcripts PPAR-γ. Altogether, these data revealed that “clinically accessible” periosteal samples represent a consistently rich source of highly proliferative MSCs compared to donor-matched BM, which importantly show similar osteochondral capacity and lower adipogenic potential. Live cell tracking allowed determination of unique morphological and migration characteristics of periosteal MSCs that can be used for the development of novel bone graft substitutes to be preferentially repopulated by these cells.
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Cruz T, López-Giraldo A, Noell G, Guirao A, Casas-Recasens S, Garcia T, Saco A, Sellares J, Agustí A, Faner R. Smoking Impairs the Immunomodulatory Capacity of Lung-Resident Mesenchymal Stem Cells in Chronic Obstructive Pulmonary Disease. Am J Respir Cell Mol Biol 2019; 61:575-583. [DOI: 10.1165/rcmb.2018-0351oc] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Affiliation(s)
- Tamara Cruz
- Centro Investigación Biomédica en Red Enfermedades Respiratorias, Barcelona, Spain
| | - Alejandra López-Giraldo
- Centro Investigación Biomédica en Red Enfermedades Respiratorias, Barcelona, Spain
- Respiratory Institute, Hospital Clinic, University of Barcelona, Barcelona, Spain
| | - Guillaume Noell
- Centro Investigación Biomédica en Red Enfermedades Respiratorias, Barcelona, Spain
- Institut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain; and
| | - Angela Guirao
- Respiratory Institute, Hospital Clinic, University of Barcelona, Barcelona, Spain
| | | | - Tamara Garcia
- Centro Investigación Biomédica en Red Enfermedades Respiratorias, Barcelona, Spain
| | - Adela Saco
- Department of Pathology, Hospital Clinic, Barcelona, Spain
| | - Jacobo Sellares
- Respiratory Institute, Hospital Clinic, University of Barcelona, Barcelona, Spain
- Institut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain; and
| | - Alvar Agustí
- Centro Investigación Biomédica en Red Enfermedades Respiratorias, Barcelona, Spain
- Respiratory Institute, Hospital Clinic, University of Barcelona, Barcelona, Spain
- Institut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain; and
| | - Rosa Faner
- Centro Investigación Biomédica en Red Enfermedades Respiratorias, Barcelona, Spain
- Institut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain; and
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Faner R, Rojas M. Building Strong Neighborhoods in the Lung with a Little Help from My Mesenchymal Stem Cells. Am J Respir Crit Care Med 2019; 199:1176-1178. [PMID: 30557513 PMCID: PMC6519862 DOI: 10.1164/rccm.201811-2153ed] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Affiliation(s)
- Rosa Faner
- 1 Institut d'Investigacions Biomediques August Pi i Sunyer Barcelona, Spain.,2 Centro de Investigación Biomedica en Red Enfermedades Respiratorias Madrid, Spain
| | - Mauricio Rojas
- 3 The Dorothy P. and Richard P. Simmons Center for Interstitial Lung Diseases and.,4 Division of Pulmonary, Allergy and Critical Care Medicine University of Pittsburgh Medical Center Pittsburgh, Pennsylvania
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Ge S, Jiang X, Paul D, Song L, Wang X, Pachter JS. Human ES-derived MSCs correct TNF-α-mediated alterations in a blood-brain barrier model. Fluids Barriers CNS 2019; 16:18. [PMID: 31256757 PMCID: PMC6600885 DOI: 10.1186/s12987-019-0138-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2018] [Accepted: 05/27/2019] [Indexed: 02/07/2023] Open
Abstract
Background Immune cell trafficking into the CNS is considered to contribute to pathogenesis in MS and its animal model, EAE. Disruption of the blood–brain barrier (BBB) is a hallmark of these pathologies and a potential target of therapeutics. Human embryonic stem cell-derived mesenchymal stem/stromal cells (hES-MSCs) have shown superior therapeutic efficacy, compared to bone marrow-derived MSCs, in reducing clinical symptoms and neuropathology of EAE. However, it has not yet been reported whether hES-MSCs inhibit and/or repair the BBB damage associated with neuroinflammation that accompanies EAE. Methods BMECs were cultured on Transwell inserts as a BBB model for all the experiments. Disruption of BBB models was induced by TNF-α, a pro-inflammatory cytokine that is a hallmark of acute and chronic neuroinflammation. Results Results indicated that hES-MSCs reversed the TNF-α-induced changes in tight junction proteins, permeability, transendothelial electrical resistance, and expression of adhesion molecules, especially when these cells were placed in direct contact with BMEC. Conclusions hES-MSCs and/or products derived from them could potentially serve as novel therapeutics to repair BBB disturbances in MS. Electronic supplementary material The online version of this article (10.1186/s12987-019-0138-5) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Shujun Ge
- Blood-Brain Barrier Laboratory, Dept. of Immunology, UConn Health, 263 Farmington Ave, Farmington, CT, 06030, USA.
| | - Xi Jiang
- Blood-Brain Barrier Laboratory, Dept. of Immunology, UConn Health, 263 Farmington Ave, Farmington, CT, 06030, USA.,Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA, 19104, USA
| | - Debayon Paul
- Blood-Brain Barrier Laboratory, Dept. of Immunology, UConn Health, 263 Farmington Ave, Farmington, CT, 06030, USA
| | - Li Song
- ImStem Biotechnology, Inc., 400 Farmington Ave., Farmington, CT, 06030, USA
| | - Xiaofang Wang
- ImStem Biotechnology, Inc., 400 Farmington Ave., Farmington, CT, 06030, USA
| | - Joel S Pachter
- Blood-Brain Barrier Laboratory, Dept. of Immunology, UConn Health, 263 Farmington Ave, Farmington, CT, 06030, USA
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Advances in Perianal Disease Associated with Crohn's Disease-Evolving Approaches. Gastrointest Endosc Clin N Am 2019; 29:515-530. [PMID: 31078250 DOI: 10.1016/j.giec.2019.02.011] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Perianal diseases, common complications of Crohn's disease, are difficult to diagnose/manage. Patients with perianal Crohn's disease suffer from persistent pain and drainage, recurrent perianal sepsis, impaired quality of life, and financial burden. Conventional medical and surgical therapies carry risk of infection, myelosuppression, incontinence, disease recurrence. Although the phenotype of Crohn's disease has been extensively studied, reported outcomes are inconsistent. Endoanal ultrasonography is also becoming popular because of low cost and ability to acquire images in real time. Emerging management strategies for treatment including laser therapy, local injection of agents, use of hyperbaric oxygen, and stem cell therapy, have demonstrated efficacy.
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Raileanu VN, Whiteley J, Chow T, Kollara A, Mohamed A, Keating A, Rogers IM. Banking Mesenchymal Stromal Cells from Umbilical Cord Tissue: Large Sample Size Analysis Reveals Consistency Between Donors. Stem Cells Transl Med 2019; 8:1041-1054. [PMID: 31219684 PMCID: PMC6766691 DOI: 10.1002/sctm.19-0022] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2019] [Accepted: 05/07/2019] [Indexed: 12/13/2022] Open
Abstract
Mesenchymal stromal cells (MSCs) have emerged as candidate cells with therapeutic potential to treat different pathologies. The underlying mechanism is paracrine signaling. The cells secrete proteins that can impact inflammation, apoptosis, angiogenesis, and cell proliferation. All are important in wound healing and tissue regeneration. Although the bone marrow has been the most widely used source of MSCs, umbilical cord tissue (CT) presents a source that is just starting to be used in the clinic, yet can be obtained with more ease and easily stored. Here, we characterize CT‐MSCs obtained from multiple donors by analyzing cell surface proteins, differentiation capacity, and proteome profile. Analysis of low, medium, and high passage cells indicates that the morphology and proliferation rate stay constant and with the exception of cluster of differentiation (CD) 105 at late passage, there are no changes in the cell surface protein characteristics, indicating the population does not change with passage. TNF‐stimulated gene 6 protein was measured in a subset of samples and variable expression was observed, but this did not impact the ability of the cells to enhance skin regeneration. In conclusion, CT‐MSC represents a consistent, easily accessible source of cells for cell therapy. stem cells translational medicine2019;8:1041–1054
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Affiliation(s)
- Vanessa N Raileanu
- Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada
| | - Jennifer Whiteley
- Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada
| | - Theresa Chow
- Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.,Department of Physiology, University of Toronto, Toronto, Ontario, Canada
| | - Alexandra Kollara
- Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada
| | - Aisha Mohamed
- Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.,Department of Physiology, University of Toronto, Toronto, Ontario, Canada
| | - Armand Keating
- Krembil Research Institute, Cancer Clinical Research Unit (CCRU), Princess Margaret Cancer Centre, Cell Therapy Program, Princess Margaret Hospital, Toronto, Canada
| | - Ian M Rogers
- Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.,Department of Physiology, University of Toronto, Toronto, Ontario, Canada.,Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, Canada
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Jervis M, Huaman O, Cahuascanco B, Bahamonde J, Cortez J, Arias JI, Torres CG, Peralta OA. Comparative analysis of in vitro proliferative, migratory and pro-angiogenic potentials of bovine fetal mesenchymal stem cells derived from bone marrow and adipose tissue. Vet Res Commun 2019; 43:165-178. [PMID: 31201618 DOI: 10.1007/s11259-019-09757-9] [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: 02/27/2019] [Accepted: 05/24/2019] [Indexed: 12/19/2022]
Abstract
Mesenchymal stem cells (MSCs) are found in virtually all tissues, where they self-renew and differentiate into multiple cell types. Cumulative data indicate that MSCs secrete paracrine factors that may play key roles in the treatment of various acute and chronic pathological conditions in diverse animal species including cattle. The aim of the present study was to compare the potentials for proliferation, migration and pro-angiogenesis of bovine fetal BM-MSCs and AT-MSCs under in vitro conditions. Growth curves and population doubling time (PDT) were determined for BM-MSCs and AT-MSCs in order to compare in vitro cell proliferation potentials. The ability of BM-MSCs and AT-MSCs to migrate was evaluated by scratch plate and transwell migration assays. The pro-angiogenic potential of conditioned medium from BM-MSCs and AT-MSCs was compared using an endothelial cell (EC) tubule formation assay. BM-MSCs displayed higher proliferation curves and doubled their populations in fewer days compared to AT-MSCs. No significant differences were detected in the number of migrant cells between BM-MSCs and AT-MSCs; however, a higher migration value was detected for BM-MSCs compared to fibroblasts (FBs), and a higher number of migrant cells were attracted by DMEM supplemented with 5% fetal bovine serum (FBS) compared to stromal cell-derived factor-1 (SDF-1). More tubules of ECs were formed after exposure to concentrated conditioned medium from AT-MSCs compared to BM-MSCs, FBs or DMEM controls. Despite common mesodermal origin, BM-MSCs display higher proliferative capacity and lower pro-angiogenic potential compared to AT-MSCs; however, both cell types possess similar migratory ability.
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Affiliation(s)
- M Jervis
- Department of Animal Production Science, Faculty of Veterinary Sciences, University of Chile, 8820808, Santiago, Chile
| | - O Huaman
- Department of Animal Production Science, Faculty of Veterinary Sciences, University of Chile, 8820808, Santiago, Chile
| | - B Cahuascanco
- Department of Animal Production Science, Faculty of Veterinary Sciences, University of Chile, 8820808, Santiago, Chile
| | - J Bahamonde
- Department of Animal Production Science, Faculty of Veterinary Sciences, University of Chile, 8820808, Santiago, Chile.,Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, 24060, USA.,Institute of Pharmacology and Morphophysiology, Faculty of Veterinary Sciences, Austral University of Chile, 5110566, Valdivia, Chile
| | - J Cortez
- Department of Animal Production Science, Faculty of Veterinary Sciences, University of Chile, 8820808, Santiago, Chile
| | - J I Arias
- Department of Clinical Science, Faculty of Veterinary Sciences, University of Chile, 8820808, Santiago, Chile
| | - C G Torres
- Department of Clinical Science, Faculty of Veterinary Sciences, University of Chile, 8820808, Santiago, Chile
| | - O A Peralta
- Department of Animal Production Science, Faculty of Veterinary Sciences, University of Chile, 8820808, Santiago, Chile. .,Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, 24060, USA.
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47
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Gnani D, Crippa S, della Volpe L, Rossella V, Conti A, Lettera E, Rivis S, Ometti M, Fraschini G, Bernardo ME, Di Micco R. An early-senescence state in aged mesenchymal stromal cells contributes to hematopoietic stem and progenitor cell clonogenic impairment through the activation of a pro-inflammatory program. Aging Cell 2019; 18:e12933. [PMID: 30828977 PMCID: PMC6516180 DOI: 10.1111/acel.12933] [Citation(s) in RCA: 123] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2018] [Revised: 01/22/2019] [Accepted: 02/02/2019] [Indexed: 12/14/2022] Open
Abstract
Hematopoietic stem and progenitor cells (HSPC) reside in the bone marrow (BM) niche and serve as a reservoir for mature blood cells throughout life. Aging in the BM is characterized by low‐grade chronic inflammation that could contribute to the reduced functionality of aged HSPC. Mesenchymal stromal cells (MSC) in the BM support HSPC self‐renewal. However, changes in MSC function with age and the crosstalk between MSC and HSPC remain understudied. Here, we conducted an extensive characterization of senescence features in BM‐derived MSC from young and aged healthy donors. Aged MSC displayed an enlarged senescent‐like morphology, a delayed clonogenic potential and reduced proliferation ability when compared to younger counterparts. Of note, the observed proliferation delay was associated with increased levels of SA‐β‐galactosidase (SA‐β‐Gal) and lipofuscin in aged MSC at early passages and a modest but consistent accumulation of physical DNA damage and DNA damage response (DDR) activation. Consistent with the establishment of a senescence‐like state in aged MSC, we detected an increase in pro‐inflammatory senescence‐associated secretory phenotype (SASP) factors, both at the transcript and protein levels. Conversely, the immunomodulatory properties of aged MSC were significantly reduced. Importantly, exposure of young HSPC to factors secreted by aged MSC induced pro‐inflammatory genes in HSPC and impaired HSPC clonogenic potential in a SASP‐dependent manner. Altogether, our results reveal that BM‐derived MSC from aged healthy donors display features of senescence and that, during aging, MSC‐associated secretomes contribute to activate an inflammatory transcriptional program in HSPC that may ultimately impair their functionality.
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Affiliation(s)
- Daniela Gnani
- San Raffaele Telethon Institute for Gene Therapy Milan Italy
| | - Stefania Crippa
- San Raffaele Telethon Institute for Gene Therapy Milan Italy
| | - Lucrezia della Volpe
- San Raffaele Telethon Institute for Gene Therapy Milan Italy
- Vita‐Salute San Raffaele University Milan Italy
| | | | - Anastasia Conti
- San Raffaele Telethon Institute for Gene Therapy Milan Italy
| | - Emanuele Lettera
- San Raffaele Telethon Institute for Gene Therapy Milan Italy
- Vita‐Salute San Raffaele University Milan Italy
| | - Silvia Rivis
- San Raffaele Telethon Institute for Gene Therapy Milan Italy
| | - Marco Ometti
- Department of Orthopedics and Traumatology San Raffaele Hospital Scientific Institute Milan Italy
| | - Gianfranco Fraschini
- Department of Orthopedics and Traumatology San Raffaele Hospital Scientific Institute Milan Italy
| | - Maria Ester Bernardo
- San Raffaele Telethon Institute for Gene Therapy Milan Italy
- Pediatric Immunohematology and Bone Marrow Transplantation Unit San Raffaele Scientific Institute Milan Italy
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Nourian Dehkordi A, Mirahmadi Babaheydari F, Chehelgerdi M, Raeisi Dehkordi S. Skin tissue engineering: wound healing based on stem-cell-based therapeutic strategies. Stem Cell Res Ther 2019; 10:111. [PMID: 30922387 PMCID: PMC6440165 DOI: 10.1186/s13287-019-1212-2] [Citation(s) in RCA: 301] [Impact Index Per Article: 50.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Normal wound healing is a dynamic and complex multiple phase process involving coordinated interactions between growth factors, cytokines, chemokines, and various cells. Any failure in these phases may lead wounds to become chronic and have abnormal scar formation. Chronic wounds affect patients' quality of life, since they require repetitive treatments and incur considerable medical costs. Thus, much effort has been focused on developing novel therapeutic approaches for wound treatment. Stem-cell-based therapeutic strategies have been proposed to treat these wounds. They have shown considerable potential for improving the rate and quality of wound healing and regenerating the skin. However, there are many challenges for using stem cells in skin regeneration. In this review, we present some sets of the data published on using embryonic stem cells, induced pluripotent stem cells, and adult stem cells in healing wounds. Additionally, we will discuss the different angles whereby these cells can contribute to their unique features and show the current drawbacks.
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Affiliation(s)
- Azar Nourian Dehkordi
- Department of Stem Cell and Regenerative Medicine, Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran
| | - Fatemeh Mirahmadi Babaheydari
- Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Mohammad Chehelgerdi
- Biotechnology Research Center, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran
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Wang X, Lin Q, Zhang T, Wang X, Cheng K, Gao M, Xia P, Li X. Low-intensity pulsed ultrasound promotes chondrogenesis of mesenchymal stem cells via regulation of autophagy. Stem Cell Res Ther 2019; 10:41. [PMID: 30670079 PMCID: PMC6343259 DOI: 10.1186/s13287-019-1142-z] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2018] [Revised: 12/28/2018] [Accepted: 01/08/2019] [Indexed: 02/07/2023] Open
Abstract
Background Low-intensity pulsed ultrasound (LIPUS) can induce mesenchymal stem cell (MSC) differentiation, although the mechanism of its potential effects on chondrogenic differentiation is unknown. Since autophagy is known to regulate the differentiation of MSCs, the aim of our study was to determine whether LIPUS induced chondrogenesis via autophagy regulation. Methods MSCs were isolated from the rat bone marrow, cultured in either standard or chondrogenic medium, and stimulated with 3 MHz of LIPUS given in 20% on–off cycles, with or without prior addition of an autophagy inhibitor or agonist. Chondrogenesis was evaluated on the basis of aggrecan (AGG) organization and the amount of type II collagen (COL2) and the mRNA expression of AGG, COL2, and SRY-related high mobility group-box gene 9 (SOX9) genes. Results LIPUS promoted the chondrogenic differentiation of MSCs, as shown by the changes in the extracellular matrix (ECM) proteins and upregulation of chondrogenic genes, and these effects were respectively augmented and inhibited by the autophagy inhibitor and agonist. Conclusions Taken together, these results indicate that LIPUS promotes MSC chondrogenesis by inhibiting autophagy.
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Affiliation(s)
- Xiaoju Wang
- Department of Rehabilitation Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China
| | - Qiang Lin
- Department of Rehabilitation Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China
| | - Tingting Zhang
- Department of Rehabilitation Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China
| | - Xinwei Wang
- Department of Rehabilitation Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China
| | - Kai Cheng
- Department of Rehabilitation Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China
| | - Mingxia Gao
- Department of Rehabilitation Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China
| | - Peng Xia
- Department of Rehabilitation Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China.
| | - Xueping Li
- Department of Rehabilitation Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China.
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Kaneko T, Gu B, Sone PP, Zaw SYM, Murano H, Zaw ZCT, Okiji T. Dental Pulp Tissue Engineering Using Mesenchymal Stem Cells: a Review with a Protocol. Stem Cell Rev Rep 2018; 14:668-676. [PMID: 29804171 DOI: 10.1007/s12015-018-9826-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Mesenchymal stem cells (MSCs) are adult stem cells that can be isolated from human and animal sources such as rats. Recently, an in vivo protocol for pulp tissue engineering using implantation of bone marrow MSCs into rat pulpotomized molars was established by our research group. This coronal pulp regeneration model showed almost complete regeneration/healing with dentin bridge formation when the cavity was sealed with mineral trioxide aggregate (MTA) to create a biocompatible seal of the pulp. This method is a powerful tool for elucidating the processes of dental pulp tissue regeneration following implantation of MSCs. In the present review, we discuss the literature in the field of dental pulp tissue engineering using MSCs including dental pulp stem cells and stem cells from exfoliated deciduous teeth. In addition, we present a brief step-by-step protocol of the coronal pulp regeneration model focusing on the implantation of rat bone marrow MSCs, biodegradable scaffolds, and hydrogels in pulpotomized rat molars. The protocol may lay the foundation for studies aiming at defining further histological and molecular mechanism of the rat pulp tissue engineering.
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Affiliation(s)
- Tomoatsu Kaneko
- Department of Pulp Biology and Endodontics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Yushima 1-5-45, Bunkyo-Ku, Tokyo, 113-8549, Japan.
| | - Bin Gu
- Department of Pulp Biology and Endodontics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Yushima 1-5-45, Bunkyo-Ku, Tokyo, 113-8549, Japan
| | - Phyo Pyai Sone
- Department of Pulp Biology and Endodontics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Yushima 1-5-45, Bunkyo-Ku, Tokyo, 113-8549, Japan
| | - Su Yee Myo Zaw
- Department of Pulp Biology and Endodontics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Yushima 1-5-45, Bunkyo-Ku, Tokyo, 113-8549, Japan
| | - Hiroki Murano
- Department of Pulp Biology and Endodontics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Yushima 1-5-45, Bunkyo-Ku, Tokyo, 113-8549, Japan
| | - Zar Chi Thein Zaw
- Department of Pulp Biology and Endodontics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Yushima 1-5-45, Bunkyo-Ku, Tokyo, 113-8549, Japan
| | - Takashi Okiji
- Department of Pulp Biology and Endodontics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Yushima 1-5-45, Bunkyo-Ku, Tokyo, 113-8549, Japan
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