miRNAs in Extracellular Vesicles from iPS-Derived Cardiac Progenitor Cells Effectively Reduce Fibrosis and Promote Angiogenesis in Infarcted Heart

Cardiac stem cell therapy offers the potential to ameliorate postinfarction remodeling and development of heart failure but requires optimization of cell-based approaches. Cardiac progenitor cells (CPCs) induction by ISX-9, a small molecule possessing antioxidant, prosurvival, and regenerative prope...

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Main Authors: Wanling Xuan, Lei Wang, Meifeng Xu, Neal L. Weintraub, Muhammad Ashraf
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2019/3726392
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author Wanling Xuan
Lei Wang
Meifeng Xu
Neal L. Weintraub
Muhammad Ashraf
author_facet Wanling Xuan
Lei Wang
Meifeng Xu
Neal L. Weintraub
Muhammad Ashraf
author_sort Wanling Xuan
collection DOAJ
description Cardiac stem cell therapy offers the potential to ameliorate postinfarction remodeling and development of heart failure but requires optimization of cell-based approaches. Cardiac progenitor cells (CPCs) induction by ISX-9, a small molecule possessing antioxidant, prosurvival, and regenerative properties, represents an attractive potential approach for cell-based cardiac regenerative therapy. Here, we report that extracellular vesicles (EV) secreted by ISX-9-induced CPCs (EV-CPCISX-9) faithfully recapitulate the beneficial effects of their parent CPCs with regard to postinfarction remodeling. These EV contain a distinct repertoire of biologically active miRNAs that promoted angiogenesis and proliferation of cardiomyocytes while ameliorating fibrosis in the infarcted heart. Amongst the highly enriched miRNAs, miR-373 was strongly antifibrotic, targeting 2 key fibrogenic genes, GDF-11 and ROCK-2. miR-373 mimic itself was highly efficacious in preventing scar formation in the infarcted myocardium. Together, these novel findings have important implications with regard to prevention of postinfarction remodeling.
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institution Kabale University
issn 1687-966X
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publishDate 2019-01-01
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series Stem Cells International
spelling doaj-art-d3f682f0b18042b78bded3c958d313dd2025-02-03T06:01:30ZengWileyStem Cells International1687-966X1687-96782019-01-01201910.1155/2019/37263923726392miRNAs in Extracellular Vesicles from iPS-Derived Cardiac Progenitor Cells Effectively Reduce Fibrosis and Promote Angiogenesis in Infarcted HeartWanling Xuan0Lei Wang1Meifeng Xu2Neal L. Weintraub3Muhammad Ashraf4Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, Georgia, USADepartment of Pharmacology, University of Illinois at Chicago College of Medicine, Chicago, Illinois, USADepartment of Pathology and Laboratory Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio, USAVascular Biology Center, Medical College of Georgia at Augusta University, Augusta, Georgia, USAVascular Biology Center, Medical College of Georgia at Augusta University, Augusta, Georgia, USACardiac stem cell therapy offers the potential to ameliorate postinfarction remodeling and development of heart failure but requires optimization of cell-based approaches. Cardiac progenitor cells (CPCs) induction by ISX-9, a small molecule possessing antioxidant, prosurvival, and regenerative properties, represents an attractive potential approach for cell-based cardiac regenerative therapy. Here, we report that extracellular vesicles (EV) secreted by ISX-9-induced CPCs (EV-CPCISX-9) faithfully recapitulate the beneficial effects of their parent CPCs with regard to postinfarction remodeling. These EV contain a distinct repertoire of biologically active miRNAs that promoted angiogenesis and proliferation of cardiomyocytes while ameliorating fibrosis in the infarcted heart. Amongst the highly enriched miRNAs, miR-373 was strongly antifibrotic, targeting 2 key fibrogenic genes, GDF-11 and ROCK-2. miR-373 mimic itself was highly efficacious in preventing scar formation in the infarcted myocardium. Together, these novel findings have important implications with regard to prevention of postinfarction remodeling.http://dx.doi.org/10.1155/2019/3726392
spellingShingle Wanling Xuan
Lei Wang
Meifeng Xu
Neal L. Weintraub
Muhammad Ashraf
miRNAs in Extracellular Vesicles from iPS-Derived Cardiac Progenitor Cells Effectively Reduce Fibrosis and Promote Angiogenesis in Infarcted Heart
Stem Cells International
title miRNAs in Extracellular Vesicles from iPS-Derived Cardiac Progenitor Cells Effectively Reduce Fibrosis and Promote Angiogenesis in Infarcted Heart
title_full miRNAs in Extracellular Vesicles from iPS-Derived Cardiac Progenitor Cells Effectively Reduce Fibrosis and Promote Angiogenesis in Infarcted Heart
title_fullStr miRNAs in Extracellular Vesicles from iPS-Derived Cardiac Progenitor Cells Effectively Reduce Fibrosis and Promote Angiogenesis in Infarcted Heart
title_full_unstemmed miRNAs in Extracellular Vesicles from iPS-Derived Cardiac Progenitor Cells Effectively Reduce Fibrosis and Promote Angiogenesis in Infarcted Heart
title_short miRNAs in Extracellular Vesicles from iPS-Derived Cardiac Progenitor Cells Effectively Reduce Fibrosis and Promote Angiogenesis in Infarcted Heart
title_sort mirnas in extracellular vesicles from ips derived cardiac progenitor cells effectively reduce fibrosis and promote angiogenesis in infarcted heart
url http://dx.doi.org/10.1155/2019/3726392
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AT neallweintraub mirnasinextracellularvesiclesfromipsderivedcardiacprogenitorcellseffectivelyreducefibrosisandpromoteangiogenesisininfarctedheart
AT muhammadashraf mirnasinextracellularvesiclesfromipsderivedcardiacprogenitorcellseffectivelyreducefibrosisandpromoteangiogenesisininfarctedheart