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

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). ME...

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Autores principales: Guo, Rui, Wan, Feng, Morimatsu, Masatoshi, Xu, Qing, Feng, Tian, Yang, Hang, Gong, Yichen, Ma, Shuhong, Chang, Yun, Zhang, Siyao, Jiang, Youxu, Wang, Heqing, Chang, Dehua, Zhang, Hongjia, Ling, Yunpeng, Lan, Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: KeAi Publishing 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941025/
https://www.ncbi.nlm.nih.gov/pubmed/33732969
http://dx.doi.org/10.1016/j.bioactmat.2021.01.036
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author Guo, Rui
Wan, Feng
Morimatsu, Masatoshi
Xu, Qing
Feng, Tian
Yang, Hang
Gong, Yichen
Ma, Shuhong
Chang, Yun
Zhang, Siyao
Jiang, Youxu
Wang, Heqing
Chang, Dehua
Zhang, Hongjia
Ling, Yunpeng
Lan, Feng
author_facet Guo, Rui
Wan, Feng
Morimatsu, Masatoshi
Xu, Qing
Feng, Tian
Yang, Hang
Gong, Yichen
Ma, Shuhong
Chang, Yun
Zhang, Siyao
Jiang, Youxu
Wang, Heqing
Chang, Dehua
Zhang, Hongjia
Ling, Yunpeng
Lan, Feng
author_sort Guo, Rui
collection PubMed
description 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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spelling pubmed-79410252021-03-16 Cell sheet formation enhances the therapeutic effects of human umbilical cord mesenchymal stem cells on myocardial infarction as a bioactive material Guo, Rui Wan, Feng Morimatsu, Masatoshi Xu, Qing Feng, Tian Yang, Hang Gong, Yichen Ma, Shuhong Chang, Yun Zhang, Siyao Jiang, Youxu Wang, Heqing Chang, Dehua Zhang, Hongjia Ling, Yunpeng Lan, Feng Bioact Mater Article 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. KeAi Publishing 2021-03-05 /pmc/articles/PMC7941025/ /pubmed/33732969 http://dx.doi.org/10.1016/j.bioactmat.2021.01.036 Text en © 2021 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Guo, Rui
Wan, Feng
Morimatsu, Masatoshi
Xu, Qing
Feng, Tian
Yang, Hang
Gong, Yichen
Ma, Shuhong
Chang, Yun
Zhang, Siyao
Jiang, Youxu
Wang, Heqing
Chang, Dehua
Zhang, Hongjia
Ling, Yunpeng
Lan, Feng
Cell sheet formation enhances the therapeutic effects of human umbilical cord mesenchymal stem cells on myocardial infarction as a bioactive material
title Cell sheet formation enhances the therapeutic effects of human umbilical cord mesenchymal stem cells on myocardial infarction as a bioactive material
title_full Cell sheet formation enhances the therapeutic effects of human umbilical cord mesenchymal stem cells on myocardial infarction as a bioactive material
title_fullStr Cell sheet formation enhances the therapeutic effects of human umbilical cord mesenchymal stem cells on myocardial infarction as a bioactive material
title_full_unstemmed Cell sheet formation enhances the therapeutic effects of human umbilical cord mesenchymal stem cells on myocardial infarction as a bioactive material
title_short Cell sheet formation enhances the therapeutic effects of human umbilical cord mesenchymal stem cells on myocardial infarction as a bioactive material
title_sort cell sheet formation enhances the therapeutic effects of human umbilical cord mesenchymal stem cells on myocardial infarction as a bioactive material
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941025/
https://www.ncbi.nlm.nih.gov/pubmed/33732969
http://dx.doi.org/10.1016/j.bioactmat.2021.01.036
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