title: Functional Effects of a Tissue-Engineered Cardiac Patch From Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes in a Rat Infarct Model.
abstract: A tissue-engineered cardiac patch provides a method to deliver cardiomyoctes to the injured myocardium with high cell retention and large, controlled infarct coverage, enhancing the ability of cells to limit remodeling after infarction. The patch environment can also yield increased survival. In the present study, we sought to assess the efficacy of a cardiac patch made from human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to engraft and limit left ventricular (LV) remodeling acutely after infarction. Cardiac patches were created from hiPSC-CMs and human pericytes (PCs) entrapped in a fibrin gel and implanted acutely onto athymic rat hearts. hiPSC-CMs not only remained viable after in vivo culture, but also increased in number by as much as twofold, consistent with colocalization of human nuclear antigen, cardiac troponin T, and Ki-67 staining. CM+PC patches led to reduced infarct sizes compared with myocardial infarction-only controls at week 4, and CM+PC patch recipient hearts exhibited greater fractional shortening over all groups at both 1 and 4 weeks after transplantation. However, a decline occurred in fractional shortening for all groups over 4 weeks, and LV thinning was not mitigated. CM+PC patches became vascularized in vivo, and microvessels were more abundant in the host myocardium border zone, suggesting a paracrine mechanism for the improved cardiac function. PCs in a PC-only control patch did not survive 4 weeks in vivo. Our results indicate that cardiac patches containing hiPSC-CMs engraft onto acute infarcts, and the hiPSC-CMs survive, proliferate, and contribute to a reduction in infarct size and improvements in cardiac function.
  
  
  CONCLUSIONS
  In the present study, a cardiac patch was created from human induced pluripotent stem cell-derived cardiomyocytes and human pericytes entrapped in a fibrin gel, and it was transplanted onto infarcted rat myocardium. It was found that a patch that contained both cardiomyocytes and pericytes survived transplantation and resulted in improved cardiac function and a reduced infarct size compared with controls.
authors.affiliation: Department of Biomedical Engineering, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: Jacqueline S
authors.initials: JS
authors.lastname: Wendel
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Ye
authors.affiliation: Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors.forename: Ran
authors.initials: R
authors.lastname: Tao
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: Jianyi
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Kamp
authors.affiliation: Department of Biomedical Engineering, University of Minnesota, Minneapolis, Minnesota, USA Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, Minnesota, USA tranquillo@umn.edu.
authors.forename: Robert T
authors.initials: RT
authors.lastname: Tranquillo
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D064593:Heterografts; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism* / Q000473:pathology; D009203:Myocardial Infarction / Q000473:pathology / Q000601:surgery*; D009206:Myocardium; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D051381:Rats; D011923:Rats, Nude
keywords: Cardiac tissue engineering; Cardiomyocyte; Fibrin; Induced pluripotent stem cell; Pericyte