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

Author:

Xuan Wanling1,Wang Lei2,Xu Meifeng3,Weintraub Neal L.1ORCID,Ashraf Muhammad1ORCID

Affiliation:

1. Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, Georgia, USA

2. Department of Pharmacology, University of Illinois at Chicago College of Medicine, Chicago, Illinois, USA

3. Department of Pathology and Laboratory Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio, USA

Abstract

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.

Funder

National Institutes of Health

Publisher

Hindawi Limited

Subject

Cell Biology,Molecular Biology

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