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

• Published in: Cell stem cell 2014-12, Vol.15 (6), p.750-761
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Acute Disease; Animals; Apoptosis; Cell Differentiation; Cell Lineage; Cells, Cultured; Disease Models, Animal; Endothelial Cells - physiology; Endothelial Cells - transplantation; Fibrin - administration & dosage; Heart Ventricles - metabolism; Heart Ventricles - pathology; Humans; Induced Pluripotent Stem Cells - physiology; Insulin-Like Growth Factor I - administration & dosage; Microspheres; Myocardial Infarction - pathology; Myocardial Infarction - therapy; Myocardium - metabolism; Myocytes, Cardiac - physiology; Myocytes, Cardiac - transplantation; Myocytes, Smooth Muscle - physiology; Myocytes, Smooth Muscle - transplantation; Recovery of Function; Stem Cell Transplantation; Swine
• ISSN: 1934-5909; 1875-9777; 1875-9777
• 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. [Display omitted] •Human iPSCs (hiPSCs) were differentiated into three cardiac lineages•hiPSC-derived cells were transplanted into a porcine model of myocardial infarction•Engraftment in combination with IGF-1-fibrin patch improves cardiac function•Intramyocardial delivery of hiPSC-cardiomyocytes did not cause arrhythmias Large animal studies are required to assess the potential of human pluripotent stem cell (hPSC)-derived cells for cardiac repair. Ye et al. show that engraftment of hiPSC-derived cardiomyocytes, endothelial cells, and smooth muscle cells into a porcine model of myocardial infarction improves heart function and metabolism without inducing ventricular arrhythmias.