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

• 作者: Hyeonju Jo Hyoung Kyu Kim Jae-Hyeong Park Jin Han Seon Pyo Hong Seungjoo Lee Sukhyun Song Sung Woo Cho
• 来源期刊: 世界干细胞杂志:英文版(电子版)
• 学科: 医学
• 关键词: PLURIPOTENT STEM CELL Embryonic STEM CELL CARDIOMYOCYTE Myocardial infarction Regeneration
• 年，卷（期）: 2019,（1）
• 页码范围: 44-54
• 页数: 11页
• 分类号: R338.3

摘要

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-α(PDGFRα)^+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 andαMHC^+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 differentiatedαMHC+^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 andαMHC+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 andαMHC^+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 intoα-actinin^+CMs,and they did not convert into CD31^+end othelial cells orαSMA^+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.