Stimulation of endogenous cardioblasts by exogenous cell therapy after myocardial infarction

Konstantinos Malliaras, Ahmed Ibrahim, Eleni Tseliou, Weixin Liu, Baiming Sun, Ryan C. Middleton, Jeffrey Seinfeld, Lai Wang, Behrooz G. Sharifi, Eduardo Marbán

Research output: Contribution to journalArticlepeer-review

69 Scopus citations


Controversy surrounds the identity, origin, and physiologic role of endogenous cardiomyocyte progenitors in adult mammals. Using an inducible genetic labeling approach to identify small non-myocyte cells expressing cardiac markers, we find that activated endogenous cardioblasts are rarely evident in the normal adult mouse heart. However, myocardial infarction results in significant cardioblast activation at the site of injury. Genetically labeled isolated cardioblasts express cardiac transcription factors and sarcomeric proteins, exhibit spontaneous contractions, and form mature cardiomyocytes in vivo after injection into unlabeled recipient hearts. The activated cardioblasts do not arise from hematogenous seeding, cardiomyocyte dedifferentiation, or mere expansion of a preformed progenitor pool. Cell therapy with cardiosphere-derived cells amplifies innate cardioblast-mediated tissue regeneration, in part through the secretion of stromal cell-derived factor 1 by transplanted cells. Thus, stimulation of endogenous cardioblasts by exogenous cells mediates therapeutic regeneration of injured myocardium.

Original languageEnglish (US)
Pages (from-to)760-777
Number of pages18
JournalEMBO Molecular Medicine
Issue number6
StatePublished - 2014
Externally publishedYes


  • Cardiac stem cells
  • Cardioblasts
  • Cardiomyocyte progenitor cells
  • Cardiosphere-derived cells
  • Heart regeneration

ASJC Scopus subject areas

  • Molecular Medicine
  • Medicine(all)


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