Regenerative potential of mouse embryonic stem cell-derived PDGFRα+ cardiac lineage committed cells in infarcted myocardium

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Title
Regenerative potential of mouse embryonic stem cell-derived PDGFRα+ cardiac lineage committed cells in infarcted myocardium
Author(s)
Seon Pyo Hong; Sukhyun Song; Lee S.; Jo H.; Kim H.K.; Han J.; Park J.-H.; Cho S.W.
Publication Date
2019-01
Journal
World Journal of Stem Cells, v.11, no.1, pp.44 - 54
Publisher
BAISHIDENG PUBLISHING GROUP INC
Abstract
BACKGROUND Pluripotent stem cell-derived cardiomyocytes (CMs) have become one of the most attractive cellular resources for cell-based therapy to rescue damaged cardiac tissue. AIM We investigated the regenerative potential of mouse embryonic stem cell (ESC)- derived platelet-derived growth factor receptor-a (DGFRα)+ cardiac lineagecommitted cells (CLCs), which have a proliferative capacity but are in a morphologically and functionally immature state compared with differentiated CMs. METHODS We induced mouse ESCs into PDGFRα+ CLCs and αMHC+ CMs using a combination of the small molecule cyclosporin A, the rho-associated coiled-coil kinase inhibitor Y27632, the antioxidant Trolox, and the ALK5 inhibitor EW7197. We implanted PDGFRα+ CLCs and differentiated αMHC+ CMs into a myocardial infarction (MI) murine model and performed functional analysis using transthoracic echocardiography (TTE) and histologic analysis. RESULTS Compared with the untreated MI hearts, the anterior and septal regional wall motion and systolic functional parameters were notably and similarly improved in the MI hearts implanted with PDGFRα+ CLCs and αMHC+ CMs based on TTE. In histologic analysis, the untreated MI hearts contained a thinner ventricular wall than did the controls, while the ventricular walls of MI hearts implanted with PDGFRα+ CLCs and αMHC+ CMs were similarly thicker compared with that of the untreated MI hearts. Furthermore, implanted PDGFRα+ CLCs aligned and integrated with host CMs and were mostly differentiated into α-actinin+ CMs, and they did not convert into CD31+ endothelial cells or aSMA+ mural cells. CONCLUSION PDGFRα+ CLCs from mouse ESCs exhibiting proliferative capacity showed a regenerative effect in infarcted myocardium. Therefore, mouse ESC-derived PDGFRα+ CLCs may represent a potential cellular resource for cardiac regeneration. © The Author(s) 2019
URI
https://pr.ibs.re.kr/handle/8788114/5767
ISSN
1948-0210
Appears in Collections:
Center for Cardiovascular Research(혈관 연구단) > Journal Papers (저널논문)
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