Cardiomyogenic potential of C-kit+-expressing cells derived from neonatal and adult mouse hearts

Marc Michael Zaruba, Mark Soonpaa, Sean Reuter, Loren J. Field

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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. Methods and 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 β-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.

Original languageEnglish (US)
Pages (from-to)1992-2000
Number of pages9
JournalCirculation
Volume121
Issue number18
DOIs
StatePublished - May 11 2010

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Keywords

  • Cardiac
  • Molecular biology
  • Myocardial infarction
  • Myocytes
  • Progenitor cells
  • Stem cells

ASJC Scopus subject areas

  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

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