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

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World Journal of Stem Cells 2019年第1期11卷 44-54页

作者： Seon Pyo Hong sukhyun song Seungjoo Lee Hyeonju Jo Hyoung Kyu Kim Jin Han Jae-Hyeong Park Sung Woo Cho Center for Vascular Research Institute of Basic Science (IBS)Daejeon Department of Neurosurgery Asan Medical Center University of Ulsan College of Medicine Cardiovascular and Metabolic Disease Center Department of Physiology Department of Health Sciences and Technology BK21 plus Project Team Inje University College of Medicine Department of Cardiology in Internal Medicine School of MedicineChungnam National University Hospital Chungnam National University Division of Cardiology Department of Internal Medicine Inje University College of Medicine Seoul Paik Hospital Cardiovascular and Metabolic Disease Center Inje University College of Medicine

BACKGROUND Pluripotent stem cell-derived cardiomyocytes(CMs) have become one of the most attractive cellular resources for cell-based therapy to rescue damaged cardiac *** We investigated the regenerative potential of mouse embryonic stem cell(ESC)-derived platelet-derived growth factor receptor-α(PDGFRα)+ cardiac lineagecommitted cells(CLCs), which have a proliferative capacity but are in a morphologically and functionally immature state compared with differentiated *** 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 *** implanted PDGFRα+ CLCs and differentiated αMHC+ CMs into a myocardial infarction(MI) murine model and performed functional analysis using transthoracic echocardiography(TTE) and histologic *** 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 *** 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 αSMA+ mural *** 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.

关键词： Pluripotent stem cell Embryonic stem cell Cardiomyocyte Myocardial infarction Regeneration

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