title: Comparison of human induced pluripotent stem-cell derived cardiomyocytes with human mesenchymal stem cells following acute myocardial infarction.
abstract: BACKGROUND
  Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have recently been shown to express key cardiac proteins and improve in vivo cardiac function when administered following myocardial infarction. However, the efficacy of hiPSC-derived cell therapies, in direct comparison to current, well-established stem cell-based therapies, is yet to be elucidated. The goal of the current study was to compare the therapeutic efficacy of human mesenchymal stem cells (hMSCs) with hiPSC-CMs in mitigating myocardial infarction (MI).
  
  
  METHODS
  Male athymic nude hyrats were subjected to permanent ligation of the left-anterior-descending (LAD) coronary artery to induce acute MI. Four experimental groups were studied: 1) control (non-MI), 2) MI, 3) hMSCs (MI+MSC), and 4) hiPSC-CMs (MI+hiPSC-derived cardiomyocytes). The hiPSC-CMs and hMSCs were labeled with superparamagnetic iron oxide (SPIO) in vitro to track the transplanted cells in the ischemic heart by high-field cardiac MRI. These cells were injected into the ischemic heart 30-min after LAD ligation. Four-weeks after MI, cardiac MRI was performed to track the transplanted cells in the infarct heart. Additionally, echocardiography (M-mode) was performed to evaluate the cardiac function. Immunohistological and western blot studies were performed to assess the cell tracking, engraftment and cardiac fibrosis in the infarct heart tissues.
  
  
  RESULTS
  Echocardiography data showed a significantly improved cardiac function in the hiPSC-CMs and hMSCs groups, when compared to MI. Immunohistological studies showed expression of connexin-43, α-actinin and myosin heavy chain in engrafted hiPSC-CMs. Cardiac fibrosis was significantly decreased in hiPSC-CMs group when compared to hMSCs or MI groups. Overall, this study demonstrated improved cardiac function with decreased fibrosis with both hiPSC-CMs and hMSCs groups when compared with MI group.
authors.affiliation: Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, 43210, United States of America; Division of Cardiovascular Medicine, The Ohio State University, Columbus, Ohio, 43210, United States of America.
authors.forename: Lucas
authors.initials: L
authors.lastname: Citro
authors.affiliation: Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, 43210, United States of America; Division of Cardiovascular Medicine, The Ohio State University, Columbus, Ohio, 43210, United States of America.
authors.forename: Shan
authors.initials: S
authors.lastname: Naidu
authors.affiliation: Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, 43210, United States of America; Division of Cardiovascular Medicine, The Ohio State University, Columbus, Ohio, 43210, United States of America.
authors.forename: Fatemat
authors.initials: F
authors.lastname: Hassan
authors.affiliation: Department of Radiology, Geisel School of Medicine at Dartmouth, Dartmouth College, New Hampshire, 03766, United States of America.
authors.forename: M Lakshmi
authors.initials: ML
authors.lastname: Kuppusamy
authors.affiliation: Department of Radiology, Geisel School of Medicine at Dartmouth, Dartmouth College, New Hampshire, 03766, United States of America.
authors.forename: Periannan
authors.initials: P
authors.lastname: Kuppusamy
authors.affiliation: Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, 43210, United States of America; Department of Emergency Medicine, The Ohio State University, Columbus, Ohio, 43210, United States of America.
authors.forename: Mark G
authors.initials: MG
authors.lastname: Angelos
authors.affiliation: Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, 43210, United States of America; Department of Emergency Medicine, The Ohio State University, Columbus, Ohio, 43210, United States of America.
authors.forename: Mahmood
authors.initials: M
authors.lastname: Khan
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004452:Echocardiography; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D009203:Myocardial Infarction / Q000473:pathology* / Q000628:therapy; D032383:Myocytes, Cardiac / Q000502:physiology*; D011923:Rats, Nude
chemical_list: D015415:Biomarkers