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

• DOI: 10.1016/j.stem.2014.11.009
• Publication Date: 2014-12-04T11:45:35Z
• Authors: Lei Ye; Ying-Hua Chang; Qiang Xiong; Pengyuan Zhang; Liying Zhang; Porur Somasundaram; Mike Lepley; Cory Swingen; Liping Su; Jacqueline S. Wendel; Jing Guo; Albert Jang; Daniel Rosenbush; Lucas Greder; James R. Dutton; Jianhua Zhang; Timothy J. Kamp; Dan S. Kaufman; Ying Ge; Jianyi Zhang
• Keywords: Swine; Cells; Heart Ventricles; Induced Pluripotent Stem Cells; Myocytes, Smooth Muscle; Myocardial Infarction; Apoptosis; Cardiovascular; Regenerative Medicine; Medical and Health Sciences; Smooth Muscle; Genetics; 2.1 Biological and endogenous factors; Animals; Humans; Cell Lineage; Myocytes, Cardiac; Aetiology; Insulin-Like Growth Factor I; Heart Disease - Coronary Heart Disease; Cells, Cultured; Transplantation; Myocytes; Fibrin; Cultured; Stem Cell Research - Induced Pluripotent Stem Cell - Human; Stem Cell Research - Induced Pluripotent Stem Cell; 5.2 Cellular and gene therapies; Animal; Myocardium; Endothelial Cells; Cell Differentiation; Cell Biology; Recovery of Function; Biological Sciences; Stem Cell Research; Microspheres; 3. Good health; Disease Models, Animal; Heart Disease; Disease Models; Acute Disease; Molecular Medicine; Development of treatments and therapeutic interventions; Cardiac; Developmental Biology; Stem Cell Transplantation

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.