In Situ Preconditioning of Human Mesenchymal Stem Cells Elicits Comprehensive Cardiac Repair Following Myocardial Infarction
Human bone marrow-derived mesenchymal stem cells (BM-MSCs), represented as a population of adult stem cells, have long been considered as one of the most promising sources for cell-based cardiac regenerative therapy. However, their clinical use has been significantly hampered by low survival and poo...
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MDPI AG
2021-02-01
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author | Woo-Sup Sim Bong-Woo Park Kiwon Ban Hun-Jun Park |
author_facet | Woo-Sup Sim Bong-Woo Park Kiwon Ban Hun-Jun Park |
author_sort | Woo-Sup Sim |
collection | DOAJ |
description | Human bone marrow-derived mesenchymal stem cells (BM-MSCs), represented as a population of adult stem cells, have long been considered as one of the most promising sources for cell-based cardiac regenerative therapy. However, their clinical use has been significantly hampered by low survival and poor retention following administration into failing hearts. Here, to improve the therapeutic effectiveness of BM-MSCs, we examined a novel therapeutic platform named in situ preconditioning in a rat myocardial infarction (MI) model. In situ preconditioning was induced by a combinatory treatment of BM-MSCs with genetically engineered hepatocyte growth factor-expressing MSCs (HGF-eMSCs) and heart-derived extracellular matrix (hdECM) hydrogel. Subsequently, our results demonstrated that in situ preconditioning with cell mixture substantially improved the survival/retention of BM-MSCs in the MI-induced rat hearts. Enhanced retention of BM-MSCs ultimately led to a significant cardiac function improvement, which was derived from the protection of myocardium and enhancement of vessel formation in the MI hearts. The results provide compelling evidence that in situ preconditioning devised to improve the therapeutic potential of BM-MSCs can be an effective strategy to achieve cardiac repair of MI hearts. |
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format | Article |
id | doaj.art-1f112f3526f74466ae8c9a0c0ba9a7af |
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issn | 1661-6596 1422-0067 |
language | English |
last_indexed | 2024-03-09T06:11:18Z |
publishDate | 2021-02-01 |
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series | International Journal of Molecular Sciences |
spelling | doaj.art-1f112f3526f74466ae8c9a0c0ba9a7af2023-12-03T11:58:07ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-02-01223144910.3390/ijms22031449In Situ Preconditioning of Human Mesenchymal Stem Cells Elicits Comprehensive Cardiac Repair Following Myocardial InfarctionWoo-Sup Sim0Bong-Woo Park1Kiwon Ban2Hun-Jun Park3Department of Biomedicine & Health Sciences, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 137701, KoreaDepartment of Biomedicine & Health Sciences, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 137701, KoreaDepartment of Biomedical Sciences, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, ChinaDepartment of Biomedicine & Health Sciences, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 137701, KoreaHuman bone marrow-derived mesenchymal stem cells (BM-MSCs), represented as a population of adult stem cells, have long been considered as one of the most promising sources for cell-based cardiac regenerative therapy. However, their clinical use has been significantly hampered by low survival and poor retention following administration into failing hearts. Here, to improve the therapeutic effectiveness of BM-MSCs, we examined a novel therapeutic platform named in situ preconditioning in a rat myocardial infarction (MI) model. In situ preconditioning was induced by a combinatory treatment of BM-MSCs with genetically engineered hepatocyte growth factor-expressing MSCs (HGF-eMSCs) and heart-derived extracellular matrix (hdECM) hydrogel. Subsequently, our results demonstrated that in situ preconditioning with cell mixture substantially improved the survival/retention of BM-MSCs in the MI-induced rat hearts. Enhanced retention of BM-MSCs ultimately led to a significant cardiac function improvement, which was derived from the protection of myocardium and enhancement of vessel formation in the MI hearts. The results provide compelling evidence that in situ preconditioning devised to improve the therapeutic potential of BM-MSCs can be an effective strategy to achieve cardiac repair of MI hearts.https://www.mdpi.com/1422-0067/22/3/1449human mesenchymal stem cellshepatocyte growth factorengineered mesenchymal stem cellsmyocardial infarctionvascular regeneration |
spellingShingle | Woo-Sup Sim Bong-Woo Park Kiwon Ban Hun-Jun Park In Situ Preconditioning of Human Mesenchymal Stem Cells Elicits Comprehensive Cardiac Repair Following Myocardial Infarction International Journal of Molecular Sciences human mesenchymal stem cells hepatocyte growth factor engineered mesenchymal stem cells myocardial infarction vascular regeneration |
title | In Situ Preconditioning of Human Mesenchymal Stem Cells Elicits Comprehensive Cardiac Repair Following Myocardial Infarction |
title_full | In Situ Preconditioning of Human Mesenchymal Stem Cells Elicits Comprehensive Cardiac Repair Following Myocardial Infarction |
title_fullStr | In Situ Preconditioning of Human Mesenchymal Stem Cells Elicits Comprehensive Cardiac Repair Following Myocardial Infarction |
title_full_unstemmed | In Situ Preconditioning of Human Mesenchymal Stem Cells Elicits Comprehensive Cardiac Repair Following Myocardial Infarction |
title_short | In Situ Preconditioning of Human Mesenchymal Stem Cells Elicits Comprehensive Cardiac Repair Following Myocardial Infarction |
title_sort | in situ preconditioning of human mesenchymal stem cells elicits comprehensive cardiac repair following myocardial infarction |
topic | human mesenchymal stem cells hepatocyte growth factor engineered mesenchymal stem cells myocardial infarction vascular regeneration |
url | https://www.mdpi.com/1422-0067/22/3/1449 |
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