title: Derivation and high engraftment of patient-specific cardiomyocyte sheet using induced pluripotent stem cells generated from adult cardiac fibroblast.
abstract: BACKGROUND
  Induced pluripotent stem cells (iPSCs) can be differentiated into potentially unlimited lineages of cell types for use in autologous cell therapy. However, the efficiency of the differentiation procedure and subsequent function of the iPSC-derived cells may be influenced by epigenetic factors that the iPSCs retain from their tissues of origin; thus, iPSC-derived cells may be more effective for treatment of myocardial injury if the iPSCs were engineered from cardiac-lineage cells, rather than dermal fibroblasts.
  
  
  RESULTS
  We show that human cardiac iPSCs (hciPSCs) can be generated from cardiac fibroblasts and subsequently differentiated into exceptionally pure (>92%) sheets of cardiomyocytes (CMs). The hciPSCs passed through all the normal stages of differentiation before assuming a CM identity. When using the fibrin gel-enhanced delivery of hciPSC-CM sheets at the site of injury in infarcted mouse hearts, the engraftment rate was 31.91%±5.75% at Day 28 post transplantation. The hciPSC-CM in the sheet also appeared to develop a more mature, structurally aligned phenotype 28 days after transplantation and was associated with significant improvements in cardiac function, vascularity, and reduction in apoptosis.
  
  
  CONCLUSIONS
  These data strongly support the potential of hciPSC-CM sheet transplantation for the treatment of heart with acute myocardial infarction.
authors.affiliation: From the Cardiovascular Division, Department of Medicine (L.Z., J.G., P.Z., Q.X., S.S.R., J.Z.), Department of Integrative Biology and Physiology, School of Medicine (S.C.W., T.D.O.C.), Stem Cell Institute and Department of Pediatrics (L.X., J.T., M.K.), and Department of Surgery (K.L.), University of Minnesota, Minneapolis, MN; and Department of Cardiology, First Affiliated Hospital, Nanjing Medical University, Nanjing, China (J.G.).
authors.forename: Liying
authors.initials: L
authors.lastname: Zhang
authors.affiliation: From the Cardiovascular Division, Department of Medicine (L.Z., J.G., P.Z., Q.X., S.S.R., J.Z.), Department of Integrative Biology and Physiology, School of Medicine (S.C.W., T.D.O.C.), Stem Cell Institute and Department of Pediatrics (L.X., J.T., M.K.), and Department of Surgery (K.L.), University of Minnesota, Minneapolis, MN; and Department of Cardiology, First Affiliated Hospital, Nanjing Medical University, Nanjing, China (J.G.).
authors.forename: Jing
authors.initials: J
authors.lastname: Guo
authors.affiliation: From the Cardiovascular Division, Department of Medicine (L.Z., J.G., P.Z., Q.X., S.S.R., J.Z.), Department of Integrative Biology and Physiology, School of Medicine (S.C.W., T.D.O.C.), Stem Cell Institute and Department of Pediatrics (L.X., J.T., M.K.), and Department of Surgery (K.L.), University of Minnesota, Minneapolis, MN; and Department of Cardiology, First Affiliated Hospital, Nanjing Medical University, Nanjing, China (J.G.).
authors.forename: Pengyuan
authors.initials: P
authors.lastname: Zhang
authors.affiliation: From the Cardiovascular Division, Department of Medicine (L.Z., J.G., P.Z., Q.X., S.S.R., J.Z.), Department of Integrative Biology and Physiology, School of Medicine (S.C.W., T.D.O.C.), Stem Cell Institute and Department of Pediatrics (L.X., J.T., M.K.), and Department of Surgery (K.L.), University of Minnesota, Minneapolis, MN; and Department of Cardiology, First Affiliated Hospital, Nanjing Medical University, Nanjing, China (J.G.).
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xiong
authors.affiliation: From the Cardiovascular Division, Department of Medicine (L.Z., J.G., P.Z., Q.X., S.S.R., J.Z.), Department of Integrative Biology and Physiology, School of Medicine (S.C.W., T.D.O.C.), Stem Cell Institute and Department of Pediatrics (L.X., J.T., M.K.), and Department of Surgery (K.L.), University of Minnesota, Minneapolis, MN; and Department of Cardiology, First Affiliated Hospital, Nanjing Medical University, Nanjing, China (J.G.).
authors.forename: Steven C
authors.initials: SC
authors.lastname: Wu
authors.affiliation: From the Cardiovascular Division, Department of Medicine (L.Z., J.G., P.Z., Q.X., S.S.R., J.Z.), Department of Integrative Biology and Physiology, School of Medicine (S.C.W., T.D.O.C.), Stem Cell Institute and Department of Pediatrics (L.X., J.T., M.K.), and Department of Surgery (K.L.), University of Minnesota, Minneapolis, MN; and Department of Cardiology, First Affiliated Hospital, Nanjing Medical University, Nanjing, China (J.G.).
authors.forename: Lily
authors.initials: L
authors.lastname: Xia
authors.affiliation: From the Cardiovascular Division, Department of Medicine (L.Z., J.G., P.Z., Q.X., S.S.R., J.Z.), Department of Integrative Biology and Physiology, School of Medicine (S.C.W., T.D.O.C.), Stem Cell Institute and Department of Pediatrics (L.X., J.T., M.K.), and Department of Surgery (K.L.), University of Minnesota, Minneapolis, MN; and Department of Cardiology, First Affiliated Hospital, Nanjing Medical University, Nanjing, China (J.G.).
authors.forename: Samit Sunny
authors.initials: SS
authors.lastname: Roy
authors.affiliation: From the Cardiovascular Division, Department of Medicine (L.Z., J.G., P.Z., Q.X., S.S.R., J.Z.), Department of Integrative Biology and Physiology, School of Medicine (S.C.W., T.D.O.C.), Stem Cell Institute and Department of Pediatrics (L.X., J.T., M.K.), and Department of Surgery (K.L.), University of Minnesota, Minneapolis, MN; and Department of Cardiology, First Affiliated Hospital, Nanjing Medical University, Nanjing, China (J.G.).
authors.forename: Jakub
authors.initials: J
authors.lastname: Tolar
authors.affiliation: From the Cardiovascular Division, Department of Medicine (L.Z., J.G., P.Z., Q.X., S.S.R., J.Z.), Department of Integrative Biology and Physiology, School of Medicine (S.C.W., T.D.O.C.), Stem Cell Institute and Department of Pediatrics (L.X., J.T., M.K.), and Department of Surgery (K.L.), University of Minnesota, Minneapolis, MN; and Department of Cardiology, First Affiliated Hospital, Nanjing Medical University, Nanjing, China (J.G.).
authors.forename: Timothy D
authors.initials: TD
authors.lastname: O'Connell
authors.affiliation: From the Cardiovascular Division, Department of Medicine (L.Z., J.G., P.Z., Q.X., S.S.R., J.Z.), Department of Integrative Biology and Physiology, School of Medicine (S.C.W., T.D.O.C.), Stem Cell Institute and Department of Pediatrics (L.X., J.T., M.K.), and Department of Surgery (K.L.), University of Minnesota, Minneapolis, MN; and Department of Cardiology, First Affiliated Hospital, Nanjing Medical University, Nanjing, China (J.G.).
authors.forename: Michael
authors.initials: M
authors.lastname: Kyba
authors.affiliation: From the Cardiovascular Division, Department of Medicine (L.Z., J.G., P.Z., Q.X., S.S.R., J.Z.), Department of Integrative Biology and Physiology, School of Medicine (S.C.W., T.D.O.C.), Stem Cell Institute and Department of Pediatrics (L.X., J.T., M.K.), and Department of Surgery (K.L.), University of Minnesota, Minneapolis, MN; and Department of Cardiology, First Affiliated Hospital, Nanjing Medical University, Nanjing, China (J.G.).
authors.forename: Kenneth
authors.initials: K
authors.lastname: Liao
authors.affiliation: From the Cardiovascular Division, Department of Medicine (L.Z., J.G., P.Z., Q.X., S.S.R., J.Z.), Department of Integrative Biology and Physiology, School of Medicine (S.C.W., T.D.O.C.), Stem Cell Institute and Department of Pediatrics (L.X., J.T., M.K.), and Department of Surgery (K.L.), University of Minnesota, Minneapolis, MN; and Department of Cardiology, First Affiliated Hospital, Nanjing Medical University, Nanjing, China (J.G.). zhang047@umn.edu.
authors.forename: Jianyi
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D005347:Fibroblasts / Q000473:pathology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000637:transplantation*; D008297:Male; D051379:Mice; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000166:cytology*; D033581:Stem Cell Transplantation / Q000379:methods*; D016896:Treatment Outcome
keywords: heart; infarction; myocardium; stem cell