Epicardial cells derived from human embryonic stem cells augment cardiomyocyte-driven heart regeneration.
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The epicardium and its derivatives provide trophic and structural support for the developing and adult heart. Here we tested the ability of human embryonic stem cell (hESC)-derived epicardium to augment the structure and function of engineered heart tissue in vitro and to improve efficacy of hESC-cardiomyocyte grafts in infarcted athymic rat hearts. Epicardial cells markedly enhanced the contractility, myofibril structure and calcium handling of human engineered heart tissues, while reducing passive stiffness compared with mesenchymal stromal cells. Transplanted epicardial cells formed persistent fibroblast grafts in infarcted hearts. Cotransplantation of hESC-derived epicardial cells and cardiomyocytes doubled graft cardiomyocyte proliferation rates in vivo, resulting in 2.6-fold greater cardiac graft size and simultaneously augmenting graft and host vascularization. Notably, cotransplantation improved systolic function compared with hearts receiving either cardiomyocytes alone, epicardial cells alone or vehicle. The ability of epicardial cells to enhance cardiac graft size and function makes them a promising adjuvant therapeutic for cardiac repair.
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1546-1696
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Medical Research Council (MR/L016761/1)
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
Addenbrooke's Charitable Trust (ACT) (Minute 23/17 B (iii))
Medical Research Council (G1000847)
Wellcome Trust (203151/Z/16/Z)
British Heart Foundation (None)
British Heart Foundation (None)
British Heart Foundation (None)
British Heart Foundation (None)
British Heart Foundation (PG/17/24/32886)
British Heart Foundation (RG/17/5/32936)
Medical Research Council (MC_PC_12009)
British Heart Foundation (SP/15/7/31561)
British Heart Foundation (PG/16/11/32021)
British Heart Foundation (FS/18/46/33663)
Stroke Association (TSA 2016/02)