title: Intramyocardial transplantation of undifferentiated rat induced pluripotent stem cells causes tumorigenesis in the heart.
abstract: BACKGROUND
  Induced pluripotent stem cells (iPSCs) are a novel candidate for use in cardiac stem cell therapy. However, their intrinsic tumorigenicity requires further investigation prior to use in a clinical setting. In this study we investigated whether undifferentiated iPSCs are tumorigenic after intramyocardial transplantation into immunocompetent allogeneic recipients.
  
  
  RESULTS
  We transplanted 2 × 10(4), 2 × 10(5), or 2 × 10(6) cells from the established rat iPSC line M13 intramyocardially into intact or infarcted hearts of immunocompetent allogeneic rats. Transplant duration was 2, 4, or 6 weeks. Histological examination with hematoxylin-eosin staining confirmed that undifferentiated rat iPSCs could generate heterogeneous tumors in both intracardiac and extracardiac sites. Furthermore, tumor incidence was independent of cell dose, transplant duration, and the presence or absence of myocardial infarction.
  
  
  CONCLUSIONS
  Our study demonstrates that allogeneic iPSC transplantation in the heart will likely result in in situ tumorigenesis, and that cells leaked from the beating heart are a potential source of tumor spread, underscoring the importance of evaluating the safety of future iPSC therapy for cardiac disease.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Yuzhen
authors.initials: Y
authors.lastname: Zhang
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.forename: Minglong
authors.initials: M
authors.lastname: Chen
authors.forename: Bing
authors.initials: B
authors.lastname: Yang
authors.forename: Fengxiang
authors.initials: F
authors.lastname: Zhang
authors.forename: Kejiang
authors.initials: K
authors.lastname: Cao
mesh_terms: D000818:Animals; D002452:Cell Count; D002454:Cell Differentiation; D002460:Cell Line; D017690:Cell Transplantation / Q000009:adverse effects*; D005260:Female; D006338:Heart Neoplasms / Q000209:etiology / Q000276:immunology / Q000473:pathology*; D007121:Immunocompetence; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000637:transplantation*; D008297:Male; D009203:Myocardial Infarction / Q000276:immunology / Q000473:pathology; D009206:Myocardium / Q000166:cytology* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014184:Transplantation, Homologous