title: Induced pluripotent stem cell transplantation in the treatment of porcine chronic myocardial ischemia.
abstract: BACKGROUND
  This study was designed to test the effects of induced pluripotent stem cell (iPSC) in the treatment of chronic myocardial ischemia.
  
  
  METHODS
  The reprogramming of passage 3 myocardial fibroblasts was performed by using the lentiviral vector containing 4 human factors: OCT4, SOX2, KLF4, and c-MYC. The iPSC colonies at P12-17 were allogeneically transplanted into ischemic myocardium of 10 swine by direct injection. Cohorts of 2 animals were sacrificed at 2, 4, 6, 8, and 12 weeks after injection.
  
  
  RESULTS
  No signs of graft versus host disease were evident at any time points. At 2 weeks, clusters of SSEA-4-positive iPSCs were detected in the injected area. At 4 to 8 weeks, these cells started to proliferate into small spheres surrounded by thin capsules. At 12 weeks the cell clusters still existed, but decreased in size and numbers. The cells inside these masses were homogeneous with no sign of differentiation into any specific lineage. Increased smooth muscle actin or vWF positive cells were found inside and around the iPSC clusters, compared with non-injected areas. By real-time polymerase chain reaction, the levels of VEGF, basic FGF, and ANRT expression were significantly higher in the iPSC-treated myocardium compared with untreated areas. These results suggest that iPSCs contributed to angiogenesis.
  
  
  CONCLUSIONS
  Allogeneically transplanted pig iPSCs proliferated despite an ischemic environment in the first 2 months and survived for at least 3 months in immunocompetent hosts. Transplanted iPSCs were also proangiogenic and thus might have beneficial effects on the ischemic heart diseases.
authors.affiliation: Cellular Biology Section, Cardiothoracic Surgery Research Program/National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland. Electronic address: zhouyifu@mail.nih.gov.
authors.forename: Yifu
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Cellular Biology Section, Cardiothoracic Surgery Research Program/National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Suna
authors.initials: S
authors.lastname: Wang
authors.affiliation: Cellular Biology Section, Cardiothoracic Surgery Research Program/National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Zuxi
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Cellular Biology Section, Cardiothoracic Surgery Research Program/National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Hoyt
authors.affiliation: Cellular Biology Section, Cardiothoracic Surgery Research Program/National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Timothy
authors.initials: T
authors.lastname: Hunt
authors.affiliation: Cellular Biology Section, Cardiothoracic Surgery Research Program/National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Bogdan
authors.initials: B
authors.lastname: Kindzelski
authors.affiliation: Cellular Biology Section, Cardiothoracic Surgery Research Program/National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: David
authors.initials: D
authors.lastname: Shou
authors.affiliation: Cellular Biology Section, Cardiothoracic Surgery Research Program/National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Wen
authors.initials: W
authors.lastname: Xie
authors.affiliation: Cellular Biology Section, Cardiothoracic Surgery Research Program/National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Yubin
authors.initials: Y
authors.lastname: Du
authors.affiliation: Cellular Biology Section, Cardiothoracic Surgery Research Program/National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Chengyu
authors.initials: C
authors.lastname: Liu
authors.affiliation: Cellular Biology Section, Cardiothoracic Surgery Research Program/National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Horvath
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000473:pathology; D000090062:Kruppel-Like Factor 4; D017202:Myocardial Ischemia / Q000473:pathology / Q000601:surgery*; D009206:Myocardium / Q000473:pathology; D039904:Pluripotent Stem Cells / Q000637:transplantation*; D033581:Stem Cell Transplantation / Q000379:methods*; D013552:Swine; D016896:Treatment Outcome