Cardiac muscle plasticity in adult and embryo by heart-derived progenitor cells

Hidemasa Oh, Xuan Chi, Steven B. Bradfute, Yuji Mishina, Jennifer Pocius, Lloyd H. Michael, Richard R. Behringer, Robert J. Schwartz, Mark L. Entman, Michael D. Schneider

Research output: Contribution to journalArticle

116 Citations (Scopus)

Abstract

The evidence of cardiomyocyte proliferation in damaged heart implied cardiac regeneration might occur by resident or extra cardiac stem cells. However, the specification and origin of these cells remain unknown. Here, we report using fluorescence-activated cell sorting that cardiac progenitor cells resided in adult heart and colocalized with small capillary vessels, within the stem cell antigen (Sca-1) population expressing high telomerase activity. Notably, hematopoietic stem cells capable of efflux Hoechst 33342, termed side population cells, also were identified within the heart-derived cells. The cardiac progenitor cells (CD45-/CD34-) express neither cardiac muscle nor endothelial cell markers at an undifferentiated stage. The exposure of 5-azacytidine induced cardiac differentiation, which depends, in part, on Bmpr1a, a type IA receptor for bone morphogenetic protein (BMP). The capability of adult Sca1+ cells to adopt a cardiac muscle in embryogenesis was substantiated by blastocyst injection, using progenitors from the adult hearts of transgenic mice that harbor a bacterial artificial chromosome expressing GFP via the Nkx-2.5 locus. Intravenously injected progenitors, shortly after ischemic/reperfusion, homed and functionally differentiated 3.5% of total left ventricle in the host myocardium. Differentiation included both fusion-independent and fusion-associated components, proved by the Cre/loxP donor/recipient system. Our studies suggest that endogenous cardiac progenitors reside in the adult heart, regenerate cardiomyocytes functionally, and integrate into the existing heart circuitry.

Original languageEnglish
Pages (from-to)182-189
Number of pages8
JournalAnnals of the New York Academy of Sciences
Volume1015
DOIs
Publication statusPublished - Jan 1 2004
Externally publishedYes

Keywords

  • Cardiac embryogenesis
  • Cell fusion
  • Myocardial regeneration

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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    Oh, H., Chi, X., Bradfute, S. B., Mishina, Y., Pocius, J., Michael, L. H., Behringer, R. R., Schwartz, R. J., Entman, M. L., & Schneider, M. D. (2004). Cardiac muscle plasticity in adult and embryo by heart-derived progenitor cells. Annals of the New York Academy of Sciences, 1015, 182-189. https://doi.org/10.1196/annals.1302.015