Stem cell-derived cell sheet transplantation for heart tissue repair in myocardial infarction

Guo, Rui; Morimatsu, Masatoshi; Tian, Feng; Lan, Feng; Chang, Dehua; Wan, Feng; Ling, Yunpeng

doi:10.1186/s13287-019-1536-y

Cited by 87 publications

(59 citation statements)

References 101 publications

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“…BMMSCs exert their paracrine effects on organ damage repair and microenvironmental and immune regulation [32] and have been shown to promote organ and tissue repair [33][34][35]. However, BMMSC therapy is limited by low colonization rate and short survival time post transplantation.…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Heme oxygenase-1-modified bone marrow mesenchymal stem cells combined with normothermic machine perfusion to protect donation after circulatory death liver grafts

et al. 2020

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Background: Donation after circulatory death (DCD) liver grafts have a poor prognosis after transplantation. We investigated whether the outcome of DCD donor organs can be improved by heme oxygenase 1 (HO-1)-modified bone marrow-derived mesenchymal stem cells (BMMSCs) combined with normothermic machine perfusion (NMP), and explored its underlying mechanisms. Methods: BMMSCs were isolated, cultured, and transduced with the HO-1 gene. An NMP system was established. DCD rat livers were obtained, preserved by different methods, and the recipients were divided into 5 groups: sham operation, static cold storage (SCS), NMP, BMMSCs combined with NMP, and HO-1/BMMSCs combined with NMP (HBP) groups. Rats were sacrificed at 1, 7, and 14 days after surgery; their blood and liver tissue samples were collected; and liver enzyme and cytokine levels, liver histology, high-mobility group box 1 (HMGB1) levels in monocytes and liver tissues, and expression of Toll-like receptor 4 (TLR4) pathway-related molecules were evaluated. Results: After liver transplantation, the SCS group showed significantly increased transaminase levels, liver tissue damage, and shorter survival time. The HBP group showed lower transaminase levels, intact liver morphology, prolonged survival time, and decreased serum and liver proinflammatory cytokine levels. In the NMP and SCS groups, HMGB1 expression in the serum, monocytes, and liver tissues and TLR4 pathway-related molecule expression were significantly decreased. Conclusions: HO-1/BMMSCs combined with NMP exerted protective effects on DCD donor liver and significantly improved recipient prognosis. The effect of HO-1/BMMSCs was greater than that of BMMSCs and was mediated via HMGB1 expression and TLR4 pathway inhibition.

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Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Heme oxygenase-1-modified bone marrow mesenchymal stem cells combined with normothermic machine perfusion to protect donation after circulatory death liver grafts

et al. 2020

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“…Cell sheet transplantation is a well-established technique that allows sheet formation of adherent cultured cells via cell–cell junctions and physical detachment from the culture dish surface under temperature differential conditions [ [20] , [21] , [22] ]. By using a cell sheet, considerably numerous cells can be stably transplanted into the damaged myocardium, depending on the cell sheet size [ [23] , [24] , [25] ].…”

Section: Introductionmentioning

confidence: 99%

Cell sheet formation enhances the therapeutic effects of human umbilical cord mesenchymal stem cells on myocardial infarction as a bioactive material

Guo

Wan

Morimatsu

et al. 2021

Bioactive Materials

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Stem cell-based therapy has been used to treat ischaemic heart diseases for two decades. However, optimal cell types and transplantation methods remain unclear. This study evaluated the therapeutic effects of human umbilical cord mesenchymal stem cell (hUCMSC) sheet on myocardial infarction (MI). Methods hUCMSCs expressing luciferase were generated by lentiviral transduction for in vivo bio-luminescent imaging tracking of cells. We applied a temperature-responsive cell culture surface-based method to form the hUCMSC sheet. Cell retention was evaluated using an in vivo bio-luminescent imaging tracking system. Unbiased transcriptional profiling of infarcted hearts and further immunohistochemical assessment of monocyte and macrophage subtypes were used to determine the mechanisms underlying the therapeutic effects of the hUCMSC sheet. Echocardiography and pathological analyses of heart sections were performed to evaluate cardiac function, angiogenesis and left ventricular remodelling. Results When transplanted to the infarcted mouse hearts, hUCMSC sheet significantly improved the retention and survival compared with cell suspension. At the early stage of MI, hUCMSC sheet modulated inflammation by decreasing Mcp1-positive monocytes and CD68-positive macrophages and increasing Cx3cr1-positive non-classical macrophages, preserving the cardiomyocytes from acute injury. Moreover, the extracellular matrix produced by hUCMSC sheet then served as bioactive scaffold for the host cells to graft and generate new epicardial tissue, providing mechanical support and routes for revascularsation. These effects of hUCMSC sheet treatment significantly improved the cardiac function at days 7 and 28 post-MI. Conclusions hUCMSC sheet formation dramatically improved the biological functions of hUCMSCs, mitigating adverse post-MI remodelling by modulating the inflammatory response and providing bioactive scaffold upon transplantation into the heart. Translational perspective Due to its excellent availability as well as superior local cellular retention and survival, allogenic transplantation of hUCMSC sheets can more effectively acquire the biological functions of hUCMSCs, such as modulating inflammation and enhancing angiogenesis. Moreover, the hUCMSC sheet method allows the transfer of an intact extracellular matrix without introducing exogenous or synthetic biomaterial, further improving its clinical applicability.

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“…The Endothelial Progenitor Cells (EPC) treatment strategy take advantages of preserving or regenerating tissue to develop towards clinical application [1][2][3]. However, the disadvantage of single cells transplantation related aggregation and necrosis make the the feasibility and effectiveness of the approach remain insu cient and di cult in clinical trials [4,5].…”

Section: Introductionmentioning

confidence: 99%

Fabrication and Paracrine Effect Research of Bone Marrow-Derived Endothelial Progenitor Cell Sheet

Xue¹,

Yin²,

Bai³

et al. 2020

Preprint

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Background: The release of a wide array of endothelial progenitor cell (EPC) sheet-secreted paracrine factors is central to the mechanism by which these cells contribute to tissue repair. The purpose of this study was to fabricate BM-EPC sheet and conduct preliminary investigation on the paracrine effect of SDF-1ɑ about the role of the stromal cell-derived factor-1α (SDF-1α)/CXCR4 axis in the form of tubular structures from BM-EPCs sheet.Methods: EPCs derived from rat bone marrow (BM-EPC) were identified and isolated by the cell-surface markers CD34/CD133/VE-cadherin/KDR using flow cytometry, as well as by dual affinity for acLDL and UEA-1. Single-cell suspensions were seeded on temperature-responsive cell culture dishes. After 7 days of incubation, the BM-EPC cells were easily harvested as cell sheets, and a series of biochemical experiments were performed in vitro. The expression levels of SDF-1α/CXCR4 axis-associated genes and proteins were examined using RT‑qPCR and western blot analysis, and enzyme-linked immunosorbent assay (ELISA) was applied to determine the concentrations of VEGF, EGF and SDF-1α in the cell culture medium.Results: The BM-EPC cell sheets were successfully harvested. Moreover, BM-EPC cell sheets have superior proliferation and tube formation activity when compare with single cell suspension. When capillary-like tube were formed from EPCs sheets, the releasing of paracrine factors such as VEGF, EGF, and SDF-1ɑ were increasing. To drive the tube formation of BM-EPCs sheets, our mechanism research showed that the activation of PI3K/AKT/eNOS pathway since the phosphorylation of protein CXCR, PI3K, AKT and eNOS were increasing. Conclusion: BM-EPC cell sheets have superior proliferation and tube formation activity that can be used for tissue repair. The strong ability to secrete paracrine factors was be related to the SDF-1α/CXCR4 axis through PI3K/AKT/eNOS pathway.

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Stem cell-derived cell sheet transplantation for heart tissue repair in myocardial infarction

Cited by 87 publications

References 101 publications

RETRACTED ARTICLE: Heme oxygenase-1-modified bone marrow mesenchymal stem cells combined with normothermic machine perfusion to protect donation after circulatory death liver grafts

RETRACTED ARTICLE: Heme oxygenase-1-modified bone marrow mesenchymal stem cells combined with normothermic machine perfusion to protect donation after circulatory death liver grafts

Cell sheet formation enhances the therapeutic effects of human umbilical cord mesenchymal stem cells on myocardial infarction as a bioactive material

Fabrication and Paracrine Effect Research of Bone Marrow-Derived Endothelial Progenitor Cell Sheet

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