title: Reprogramming of skeletal myoblasts for induction of pluripotency for tumor-free cardiomyogenesis in the infarcted heart.
abstract: BACKGROUND
  Skeletal myoblasts (SMs) with inherent myogenic properties are better candidates for reprogramming to pluripotency.
  
  
  OBJECTIVE
  To reprogram SMs to pluripotency and show that reprogrammed SMs (SiPS) express embryonic gene and microRNA profiles and that transplantation of predifferentiated cardiac progenitors reduce tumor formation.
  
  
  RESULTS
  The pMXs vector containing mouse cDNAs for Yamanaka's quartet of stemness factors were used for transduction of SMs purified from male Oct4-GFP(+) transgenic mouse. Three weeks later, GFP(+) colonies of SiPS were isolated and propagated in vitro. SiPS were positive for alkaline phosphatase, expressed SSEA1, and displayed a panel of embryonic stem (ES) cell-specific pluripotency markers. Embryoid body formation yielded beating cardiomyocyte-like cells, which expressed early and late cardiac-specific markers. SiPS also had an microRNA profile that was altered during their cardiomyogenic differentiation. Noticeable abrogation of let-7 family and significant up-regulation of miR-200a-c was observed in SiPS and SiPS-derived cardiomyocytes, respectively. In vivo studies in an experimental model of acute myocardial infarction showed extensive survival of SiPS and SiPS-derived cardiomyocytes in mouse heart after transplantation. Our results from 4-week studies in DMEM without cells (group 1), SMs (group-2), SiPS (group-3), and SiPS-derived cardiomyocytes (group 4) showed extensive myogenic integration of the transplanted cells in group 4 with attenuated infarct size and improved cardiac function without tumorgenesis.
  
  
  CONCLUSIONS
  Successful reprogramming was achieved in SMs with ES cell-like microRNA profile. Given the tumorgenic nature of SiPS, their predifferentiation into cardiomyocytes would be important for tumor-free cardiogenesis in the heart.
authors.affiliation: Department of Pathology, University of Cincinnati, Cincinnati, OH 45267-0529, USA.
authors.forename: Rafeeq P H
authors.initials: RP
authors.lastname: Ahmed
authors.forename: Husnain K
authors.initials: HK
authors.lastname: Haider
authors.forename: Stephanie
authors.initials: S
authors.lastname: Buccini
authors.forename: Longhu
authors.initials: L
authors.lastname: Li
authors.forename: Shujia
authors.initials: S
authors.lastname: Jiang
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ashraf
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D005260:Female; D006338:Heart Neoplasms / Q000517:prevention & control*; D057026:Induced Pluripotent Stem Cells / Q000637:transplantation*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000032:analysis; D024510:Muscle Development; D032448:Myoblasts, Skeletal / Q000166:cytology*; D009203:Myocardial Infarction / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000502:physiology / Q000637:transplantation*; D012038:Regeneration; D013599:Systole; D016277:Ventricular Function, Left
chemical_list: D035683:MicroRNAs