title: Cardiac repair in a porcine model of acute myocardial infarction with human induced pluripotent stem cell-derived cardiovascular cells.
abstract: 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.
authors.affiliation: Division of Cardiology, Department of Medicine, University of Minnesota, Minneapolis, MN, 55455, USA; Stem Cell Institute, University of Minnesota, Minneapolis, MN, 55455, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Ye
authors.affiliation: Department of Cell and Regenerative Biology, University of Wisconsin, Madison, WI, 53705, USA.
authors.forename: Ying-Hua
authors.initials: YH
authors.lastname: Chang
authors.affiliation: Division of Cardiology, Department of Medicine, University of Minnesota, Minneapolis, MN, 55455, USA.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xiong
authors.affiliation: Division of Cardiology, Department of Medicine, University of Minnesota, Minneapolis, MN, 55455, USA.
authors.forename: Pengyuan
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Division of Cardiology, Department of Medicine, University of Minnesota, Minneapolis, MN, 55455, USA.
authors.forename: Liying
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Division of Cardiology, Department of Medicine, University of Minnesota, Minneapolis, MN, 55455, USA.
authors.forename: Porur
authors.initials: P
authors.lastname: Somasundaram
authors.affiliation: Stem Cell Institute, University of Minnesota, Minneapolis, MN, 55455, USA; Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, 55455, USA.
authors.forename: Mike
authors.initials: M
authors.lastname: Lepley
authors.affiliation: Division of Cardiology, Department of Medicine, University of Minnesota, Minneapolis, MN, 55455, USA.
authors.forename: Cory
authors.initials: C
authors.lastname: Swingen
authors.affiliation: Division of Cardiology, Department of Medicine, University of Minnesota, Minneapolis, MN, 55455, USA.
authors.forename: Liping
authors.initials: L
authors.lastname: Su
authors.affiliation: Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN, 55455, USA.
authors.forename: Jacqueline S
authors.initials: JS
authors.lastname: Wendel
authors.affiliation: Division of Cardiology, Department of Medicine, University of Minnesota, Minneapolis, MN, 55455, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Electrical and Computer Engineering, University of Minnesota, Minneapolis, MN, 55455, USA.
authors.forename: Albert
authors.initials: A
authors.lastname: Jang
authors.affiliation: Division of Cardiology, Department of Medicine, University of Minnesota, Minneapolis, MN, 55455, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Rosenbush
authors.affiliation: Stem Cell Institute, University of Minnesota, Minneapolis, MN, 55455, USA.
authors.forename: Lucas
authors.initials: L
authors.lastname: Greder
authors.affiliation: Stem Cell Institute, University of Minnesota, Minneapolis, MN, 55455, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Dutton
authors.affiliation: Department of Medicine, University of Wisconsin, Madison, WI, 53705, USA.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Cell and Regenerative Biology, University of Wisconsin, Madison, WI, 53705, USA; Department of Medicine, University of Wisconsin, Madison, WI, 53705, USA.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Kamp
authors.affiliation: Stem Cell Institute, University of Minnesota, Minneapolis, MN, 55455, USA; Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, 55455, USA.
authors.forename: Dan S
authors.initials: DS
authors.lastname: Kaufman
authors.affiliation: Department of Cell and Regenerative Biology, University of Wisconsin, Madison, WI, 53705, USA; Department of Chemistry, University of Wisconsin, Madison, WI, 53706, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ge
authors.affiliation: 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 Biomedical Engineering, University of Minnesota, Minneapolis, MN, 55455, USA; Department of Electrical and Computer Engineering, University of Minnesota, Minneapolis, MN, 55455, USA. Electronic address: zhang047@umn.edu.
authors.forename: Jianyi
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000208:Acute Disease; D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000502:physiology / Q000637:transplantation*; D005337:Fibrin / Q000008:administration & dosage; D006352:Heart Ventricles / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage; D008863:Microspheres; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000502:physiology / Q000637:transplantation*; D032389:Myocytes, Smooth Muscle / Q000502:physiology / Q000637:transplantation*; D020127:Recovery of Function; D033581:Stem Cell Transplantation; D013552:Swine
chemical_list: D007334:Insulin-Like Growth Factor I; D005337:Fibrin