Ye Lei, Chang Ying-Hua, Xiong Qiang, Zhang Pengyuan, Zhang Liying, Somasundaram Porur, Lepley Mike, Swingen Cory, Su Liping, Wendel Jacqueline S, Guo Jing, Jang Albert, Rosenbush Daniel, Greder Lucas, Dutton James R, Zhang Jianhua, Kamp Timothy J, Kaufman Dan S, Ge Ying, Zhang Jianyi
Division of Cardiology, Department of Medicine, University of Minnesota, Minneapolis, MN, 55455, USA; Stem Cell Institute, University of Minnesota, Minneapolis, MN, 55455, USA.
Department of Cell and Regenerative Biology, University of Wisconsin, Madison, WI, 53705, USA.
Cell Stem Cell. 2014 Dec 4;15(6):750-61. doi: 10.1016/j.stem.2014.11.009.
Human induced pluripotent stem cells (hiPSCs) hold promise for myocardial repair following injury, but preclinical studies in large animal models are required to determine optimal cell preparation and delivery strategies to maximize functional benefits and to evaluate safety. Here, we utilized a porcine model of acute myocardial infarction (MI) to investigate the functional impact of intramyocardial transplantation of hiPSC-derived cardiomyocytes, endothelial cells, and smooth muscle cells, in combination with a 3D fibrin patch loaded with insulin growth factor (IGF)-encapsulated microspheres. hiPSC-derived cardiomyocytes integrated into host myocardium and generated organized sarcomeric structures, and endothelial and smooth muscle cells contributed to host vasculature. Trilineage cell transplantation significantly improved left ventricular function, myocardial metabolism, and arteriole density, while reducing infarct size, ventricular wall stress, and apoptosis without inducing ventricular arrhythmias. These findings in a large animal MI model highlight the potential of utilizing hiPSC-derived cells for cardiac repair.
人诱导多能干细胞（hiPSC）有望用于损伤后的心肌修复，但需要在大型动物模型中进行临床前研究，以确定最佳的细胞制备和递送策略，从而最大限度地提高功能效益并评估安全性。在此，我们利用猪急性心肌梗死（MI）模型，研究hiPSC来源的心肌细胞、内皮细胞和平滑肌细胞心肌内移植，联合负载胰岛素生长因子（IGF）包裹微球的三维纤维蛋白贴片的功能影响。hiPSC来源的心肌细胞整合到宿主心肌中并形成有组织的肌节结构，内皮细胞和平滑肌细胞则促进宿主血管生成。三系细胞移植显著改善了左心室功能、心肌代谢和小动脉密度，同时减小了梗死面积、心室壁应力并减少了细胞凋亡，且未诱发室性心律失常。在大型动物MI模型中的这些发现突出了利用hiPSC来源的细胞进行心脏修复的潜力。
