Cardiac Repair in a Porcine Model of Acute Myocardial Infarction with Human Induced Pluripotent Stem Cell-Derived Cardiovascular Cells

被引：389

作者：

Ye, Lei ^{[1
,2
]}

Chang, Ying-Hua ^{[3
]}

Xiong, Qiang ^{[1
]}

Zhang, Pengyuan ^{[1
]}

Zhang, Liying ^{[1
]}

Somasundaram, Porur ^{[1
]}

Lepley, Mike ^{[2
,4
]}

Swingen, Cory ^{[1
]}

Su, Liping ^{[1
]}

Wendel, Jacqueline S. ^{[5
]}

Guo, Jing ^{[1
]}

Jang, Albert ^{[6
]}

Rosenbush, Daniel ^{[1
]}

Greder, Lucas ^{[2
]}

Dutton, James R. ^{[2
]}

Zhang, Jianhua ^{[7
]}

Kamp, Timothy J. ^{[3
,7
]}

Kaufman, Dan S. ^{[2
,4
]}

Ge, Ying ^{[3
,8
]}

Zhang, Jianyi ^{[1
,2
,5
,6
]}

机构：

[1] Univ Minnesota, Dept Med, Div Cardiol, Minneapolis, MN 55455 USA

[2] Univ Minnesota, Stem Cell Inst, Minneapolis, MN 55455 USA

[3] Univ Wisconsin, Dept Cell & Regenerat Biol, Madison, WI 53705 USA

[4] Univ Minnesota, Dept Med, Div Hematol Oncol & Transplantat, Minneapolis, MN 55455 USA

[5] Univ Minnesota, Dept Biomed Engn, Minneapolis, MN 55455 USA

[6] Univ Minnesota, Dept Elect & Comp Engn, Minneapolis, MN 55455 USA

[7] Univ Wisconsin, Dept Med, Madison, WI 53705 USA

[8] Univ Wisconsin, Dept Chem, Madison, WI 53706 USA

来源：

CELL STEM CELL | 2014年 / 15卷 / 06期

关键词：

GROWTH-FACTOR-I; FUNCTIONAL CONSEQUENCES; PROGENITOR CELLS; RAT HEARTS; CARDIOMYOCYTES; THERAPY; TRANSPLANTATION; SURVIVAL; DIFFERENTIATION; PERFORMANCE;

D O I：

10.1016/j.stem.2014.11.009

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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.

引用

页码：750 / 761

页数：12

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