title: Cardiomyogenic potential of C-kit(+)-expressing cells derived from neonatal and adult mouse hearts.
abstract: BACKGROUND
  C-kit is a receptor tyrosine kinase family member expressed in hematopoietic stem cells. C-kit is also transiently expressed in cardiomyocyte precursors during development and in a rare cell population in the normal adult heart. In the present study, the cardiomyogenic potential of c-kit(+) cells isolated from normal neonatal, normal adult, and infarcted adult mouse hearts was evaluated.
  
  
  RESULTS
  Magnetic activated cell sorting was used to prepare c-kit(+) cells from the hearts of ACT-EGFP/MHC-nLAC double transgenic mice. These animals exhibit widespread enhanced green fluorescent protein (EGFP) expression and cardiomyocyte-restricted nuclear beta-galactosidase activity, thus permitting simultaneous tracking of cell survival and differentiation. A subset of the c-kit(+) cells from double transgenic neonatal hearts acquired a cardiomyogenic phenotype when cocultured with fetal cardiomyocytes (2.4% of all EGFP(+) cells screened) but rarely when cultured alone or when cocultured with mouse fibroblasts (0.03% and 0.05% of the EGFP(+) cells screened, respectively). In contrast, c-kit(+) cells from normal adult double transgenic hearts failed to undergo cardiomyogenic differentiation when cocultured with nontransgenic fetal cardiomyocytes (>18 000 EGFP(+) cells screened) or when transplanted into normal or infarcted adult mouse hearts (14 EGFP(+) grafts examined). A single c-kit(+) cell from an infarcted double transgenic adult heart was observed to acquire a cardiomyogenic phenotype in coculture (>37 000 EGFP(+) cells screened).
  
  
  CONCLUSIONS
  These data suggest that the ability of cardiac-resident c-kit(+) cells to acquire a cardiomyogenic phenotype is subject to temporal limitations or, alternatively, that the cardiomyogenic population is lost. Elucidation of the underlying molecular basis may permit robust cardiomyogenic induction in adult-derived cardiac c-kit(+) cells.
authors.affiliation: Riley Heart Research Center, Indiana University School of Medicine, Indianapolis, 46202, USA.
authors.forename: Marc-Michael
authors.initials: MM
authors.lastname: Zaruba
authors.forename: Mark
authors.initials: M
authors.lastname: Soonpaa
authors.forename: Sean
authors.initials: S
authors.lastname: Reuter
authors.forename: Loren J
authors.initials: LJ
authors.lastname: Field
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000502:physiology; D010641:Phenotype; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*
chemical_list: D049452:Green Fluorescent Proteins; D019009:Proto-Oncogene Proteins c-kit