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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| Format: | Article |
| Language: | English |
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KeAi Communications Co., Ltd.
2021-09-01
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| Series: | Bioactive Materials |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X21000487 |
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| author | Rui Guo, M.D., Ph.D. Feng Wan Masatoshi Morimatsu Qing Xu Tian Feng Hang Yang Yichen Gong Shuhong Ma Yun Chang Siyao Zhang Youxu Jiang Heqing Wang Dehua Chang Hongjia Zhang Yunpeng Ling Feng Lan |
| author_facet | Rui Guo, M.D., Ph.D. Feng Wan Masatoshi Morimatsu Qing Xu Tian Feng Hang Yang Yichen Gong Shuhong Ma Yun Chang Siyao Zhang Youxu Jiang Heqing Wang Dehua Chang Hongjia Zhang Yunpeng Ling Feng Lan |
| author_sort | Rui Guo, M.D., Ph.D. |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-24T08:28:25Z |
| format | Article |
| id | doaj.art-bd18c5dc3a2645359fecae054474b9c6 |
| institution | Directory Open Access Journal |
| issn | 2452-199X |
| language | English |
| last_indexed | 2024-04-24T08:28:25Z |
| publishDate | 2021-09-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Bioactive Materials |
| spelling | doaj.art-bd18c5dc3a2645359fecae054474b9c62024-04-16T21:11:10ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2021-09-016929993012Cell sheet formation enhances the therapeutic effects of human umbilical cord mesenchymal stem cells on myocardial infarction as a bioactive materialRui Guo, M.D., Ph.D.0Feng Wan1Masatoshi Morimatsu2Qing Xu3Tian Feng4Hang Yang5Yichen Gong6Shuhong Ma7Yun Chang8Siyao Zhang9Youxu Jiang10Heqing Wang11Dehua Chang12Hongjia Zhang13Yunpeng Ling14Feng Lan15Department of Cardiac Surgery, Peking University Third Hospital, Beijing, 100191, China; Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, 700-8558, JapanDepartment of Cardiac Surgery, Peking University Third Hospital, Beijing, 100191, China; Department of Cardiovascular Surgery, Tongji University East Hospital, Shanghai, 200120, ChinaDepartment of Cardiac Surgery, Peking University Third Hospital, Beijing, 100191, China; Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, 700-8558, JapanDepartment of Cardiac Surgery, Peking University Third Hospital, Beijing, 100191, ChinaDepartment of Cardiac Surgery, Peking University Third Hospital, Beijing, 100191, China; Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, 700-8558, JapanDepartment of Cardiac Surgery, Peking University Third Hospital, Beijing, 100191, ChinaDepartment of Cardiac Surgery, Peking University Third Hospital, Beijing, 100191, ChinaDepartment of Cardiac Surgery, Peking University Third Hospital, Beijing, 100191, China; State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, ChinaDepartment of Cardiac Surgery, Peking University Third Hospital, Beijing, 100191, China; State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, ChinaDepartment of Cardiac Surgery, Peking University Third Hospital, Beijing, 100191, China; State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, ChinaDepartment of Cardiac Surgery, Peking University Third Hospital, Beijing, 100191, China; State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, ChinaDepartment of Cardiac Surgery, Peking University Third Hospital, Beijing, 100191, China; Department of Cardiovascular Surgery, Tongji University East Hospital, Shanghai, 200120, ChinaDepartment of Cardiac Surgery, Peking University Third Hospital, Beijing, 100191, China; Department of Cardiac Surgery, The University of Tokyo Hospital, Tokyo, 113-8655, JapanDepartment of Cardiac Surgery, Peking University Third Hospital, Beijing, 100191, China; Beijing Laboratory for Cardiovascular Precision Medicine, MOE Key Laboratory of Medical Engineering for Cardiovascular Diseases, Anzhen Hospital, Capital Medical University, Beijing, 100029, ChinaDepartment of Cardiac Surgery, Peking University Third Hospital, Beijing, 100191, China; Corresponding author.Department of Cardiac Surgery, Peking University Third Hospital, Beijing, 100191, China; State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China; Fuwai Hospital Chinese Academy of Medical Sciences, Shenzhen, Shenzhen, China; Corresponding author. Department of Cardiac Surgery, Peking University Third Hospital, Beijing, 100191, China.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.http://www.sciencedirect.com/science/article/pii/S2452199X21000487Mesenchymal stem cellsCell sheetMyocardial infarctionRegulation of inflammatory responseVentricular remodelling |
| spellingShingle | Rui Guo, M.D., Ph.D. Feng Wan Masatoshi Morimatsu Qing Xu Tian Feng Hang Yang Yichen Gong Shuhong Ma Yun Chang Siyao Zhang Youxu Jiang Heqing Wang Dehua Chang Hongjia Zhang Yunpeng Ling Feng Lan Cell sheet formation enhances the therapeutic effects of human umbilical cord mesenchymal stem cells on myocardial infarction as a bioactive material Bioactive Materials Mesenchymal stem cells Cell sheet Myocardial infarction Regulation of inflammatory response Ventricular remodelling |
| 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 | Mesenchymal stem cells Cell sheet Myocardial infarction Regulation of inflammatory response Ventricular remodelling |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X21000487 |
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