Toronto General Hospital Research Institute, University Health Network, 101 College St., Toronto, ON M5G 1L7, Canada.
Division of Cardiovascular Surgery, Department of Surgery, University Health Network and University of Toronto, Toronto, ON M5G 1L7, Canada.
Sci Transl Med. 2020 Sep 23;12(562). doi: 10.1126/scitranslmed.aax2992.
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) offer an unprecedented opportunity to remuscularize infarcted human hearts. However, studies have shown that most hiPSC-CMs do not survive after transplantation into the ischemic myocardial environment, limiting their regenerative potential and clinical application. We established a method to improve hiPSC-CM survival by cotransplanting ready-made microvessels obtained from adipose tissue. Ready-made microvessels promoted a sixfold increase in hiPSC-CM survival and superior functional recovery when compared to hiPSC-CMs transplanted alone or cotransplanted with a suspension of dissociated endothelial cells in infarcted rat hearts. Microvessels showed unprecedented persistence and integration at both early (80%, week 1) and late (60%, week 4) time points, resulting in increased vessel density and graft perfusion, and improved hiPSC-CM maturation. These findings provide an approach to cell-based therapies for myocardial infarction, whereby incorporation of ready-made microvessels can improve functional outcomes in cell replacement therapies.
人诱导多能干细胞衍生的心肌细胞（hiPSC-CMs）为修复梗死的人心肌提供了前所未有的机会。然而，研究表明，大多数 hiPSC-CMs 在移植到缺血性心肌环境后无法存活，限制了它们的再生潜力和临床应用。我们建立了一种通过共移植从脂肪组织中获得的现成微血管来提高 hiPSC-CM 存活率的方法。与单独移植 hiPSC-CMs 或共移植分离的内皮细胞悬浮液相比，现成的微血管可使 hiPSC-CM 的存活率提高 6 倍，并获得更好的功能恢复。微血管在早期（约 80%，第 1 周）和晚期（约 60%，第 4 周）均表现出前所未有的持久性和整合性，导致血管密度和移植物灌注增加，以及 hiPSC-CM 成熟度提高。这些发现为心肌梗死的细胞治疗提供了一种方法，通过整合现成的微血管可以改善细胞替代治疗的功能结果。
