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Dual human iPSC-derived cardiac lineage cell-seeding extracellular matrix patches promote regeneration and long-term repair of infarcted hearts

Human pluripotent stem cell-derived cardiovascular progenitor cells (hCVPCs) and cardiomyocytes (hCMs) possess therapeutic potential for infarcted hearts; however, their efficacy needs to be enhanced. Here we tested the hypotheses that the combination of decellularized porcine small intestinal submu...

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Autores principales: Jiang, Yun, Zhang, Ling-Ling, Zhang, Fan, Bi, Wei, Zhang, Peng, Yu, Xiu-Jian, Rao, Sen-Le, Wang, Shi-Hui, Li, Qiang, Ding, Chen, Jin, Yin, Liu, Zhong-Min, Yang, Huang-Tian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: KeAi Publishing 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10236375/
https://www.ncbi.nlm.nih.gov/pubmed/37274446
http://dx.doi.org/10.1016/j.bioactmat.2023.05.015
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author Jiang, Yun
Zhang, Ling-Ling
Zhang, Fan
Bi, Wei
Zhang, Peng
Yu, Xiu-Jian
Rao, Sen-Le
Wang, Shi-Hui
Li, Qiang
Ding, Chen
Jin, Yin
Liu, Zhong-Min
Yang, Huang-Tian
author_facet Jiang, Yun
Zhang, Ling-Ling
Zhang, Fan
Bi, Wei
Zhang, Peng
Yu, Xiu-Jian
Rao, Sen-Le
Wang, Shi-Hui
Li, Qiang
Ding, Chen
Jin, Yin
Liu, Zhong-Min
Yang, Huang-Tian
author_sort Jiang, Yun
collection PubMed
description Human pluripotent stem cell-derived cardiovascular progenitor cells (hCVPCs) and cardiomyocytes (hCMs) possess therapeutic potential for infarcted hearts; however, their efficacy needs to be enhanced. Here we tested the hypotheses that the combination of decellularized porcine small intestinal submucosal extracellular matrix (SIS-ECM) with hCVPCs, hCMs, or dual of them (Mix, 1:1) could provide better therapeutic effects than the SIS alone, and dual hCVPCs with hCMs would exert synergic effects in cardiac repair. The data showed that the SIS patch well supported the growth of hCVPCs and hCMs. Epicardially implanted SIS-hCVPC, SIS-hCM, or SIS-Mix patches at 7-day post-myocardial infarction significantly ameliorated functional worsening, ventricular dilation and scar formation at 28- and 90-day post-implantation in C57/B6 mice, whereas the SIS only mildly improved function at 90-day post-implantation. Moreover, the SIS and SIS-cell patches improved vascularization and suppressed MI-induced cardiomyocyte hypertrophy and expression of Col1 and Col3, but only the SIS-hCM and the SIS-Mix patches increased the ratio of collagen III/I fibers in the infarcted hearts. Further, the SIS-cell patches stimulated cardiomyocyte proliferation via paracrine action. Notably, the SIS-Mix had better improvements in cardiac function and structure, engraftments, and cardiomyocyte proliferation. Proteomic analysis showed distinct biological functions of exclusive proteins secreted from hCVPCs and hCMs, and more exclusive proteins secreted from co-cultivated hCVPCs and hCMs than mono-cells involving in various functional processes essential for infarct repair. These findings are the first to demonstrate the efficacy and mechanisms of mono- and dual-hCVPC- and hCM-seeding SIS-ECM for repair of infarcted hearts based on the side-by-side comparison.
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spelling pubmed-102363752023-06-03 Dual human iPSC-derived cardiac lineage cell-seeding extracellular matrix patches promote regeneration and long-term repair of infarcted hearts Jiang, Yun Zhang, Ling-Ling Zhang, Fan Bi, Wei Zhang, Peng Yu, Xiu-Jian Rao, Sen-Le Wang, Shi-Hui Li, Qiang Ding, Chen Jin, Yin Liu, Zhong-Min Yang, Huang-Tian Bioact Mater Article Human pluripotent stem cell-derived cardiovascular progenitor cells (hCVPCs) and cardiomyocytes (hCMs) possess therapeutic potential for infarcted hearts; however, their efficacy needs to be enhanced. Here we tested the hypotheses that the combination of decellularized porcine small intestinal submucosal extracellular matrix (SIS-ECM) with hCVPCs, hCMs, or dual of them (Mix, 1:1) could provide better therapeutic effects than the SIS alone, and dual hCVPCs with hCMs would exert synergic effects in cardiac repair. The data showed that the SIS patch well supported the growth of hCVPCs and hCMs. Epicardially implanted SIS-hCVPC, SIS-hCM, or SIS-Mix patches at 7-day post-myocardial infarction significantly ameliorated functional worsening, ventricular dilation and scar formation at 28- and 90-day post-implantation in C57/B6 mice, whereas the SIS only mildly improved function at 90-day post-implantation. Moreover, the SIS and SIS-cell patches improved vascularization and suppressed MI-induced cardiomyocyte hypertrophy and expression of Col1 and Col3, but only the SIS-hCM and the SIS-Mix patches increased the ratio of collagen III/I fibers in the infarcted hearts. Further, the SIS-cell patches stimulated cardiomyocyte proliferation via paracrine action. Notably, the SIS-Mix had better improvements in cardiac function and structure, engraftments, and cardiomyocyte proliferation. Proteomic analysis showed distinct biological functions of exclusive proteins secreted from hCVPCs and hCMs, and more exclusive proteins secreted from co-cultivated hCVPCs and hCMs than mono-cells involving in various functional processes essential for infarct repair. These findings are the first to demonstrate the efficacy and mechanisms of mono- and dual-hCVPC- and hCM-seeding SIS-ECM for repair of infarcted hearts based on the side-by-side comparison. KeAi Publishing 2023-05-27 /pmc/articles/PMC10236375/ /pubmed/37274446 http://dx.doi.org/10.1016/j.bioactmat.2023.05.015 Text en © 2023 The Authors https://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
Jiang, Yun
Zhang, Ling-Ling
Zhang, Fan
Bi, Wei
Zhang, Peng
Yu, Xiu-Jian
Rao, Sen-Le
Wang, Shi-Hui
Li, Qiang
Ding, Chen
Jin, Yin
Liu, Zhong-Min
Yang, Huang-Tian
Dual human iPSC-derived cardiac lineage cell-seeding extracellular matrix patches promote regeneration and long-term repair of infarcted hearts
title Dual human iPSC-derived cardiac lineage cell-seeding extracellular matrix patches promote regeneration and long-term repair of infarcted hearts
title_full Dual human iPSC-derived cardiac lineage cell-seeding extracellular matrix patches promote regeneration and long-term repair of infarcted hearts
title_fullStr Dual human iPSC-derived cardiac lineage cell-seeding extracellular matrix patches promote regeneration and long-term repair of infarcted hearts
title_full_unstemmed Dual human iPSC-derived cardiac lineage cell-seeding extracellular matrix patches promote regeneration and long-term repair of infarcted hearts
title_short Dual human iPSC-derived cardiac lineage cell-seeding extracellular matrix patches promote regeneration and long-term repair of infarcted hearts
title_sort dual human ipsc-derived cardiac lineage cell-seeding extracellular matrix patches promote regeneration and long-term repair of infarcted hearts
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10236375/
https://www.ncbi.nlm.nih.gov/pubmed/37274446
http://dx.doi.org/10.1016/j.bioactmat.2023.05.015
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