Cardiac progenitor cells from adult myocardium: Homing, differentiation, and fusion after infarction

Hidemasa Oh, Steven B. Bradfute, Teresa D. Gallardo, Teruya Nakamura, Vinciane Gaussin, Yuji Mishina, Jennifer Pocius, Lloyd H. Michael, Richard R. Behringer, Daniel J. Garry, Mark L. Entman, Michael D. Schneider

Research output: Contribution to journalArticlepeer-review

1437 Scopus citations

Abstract

Potential repair by cell grafting or mobilizing endogenous cells holds particular attraction in heart disease, where the meager capacity for cardiomyocyte proliferation likely contributes to the irreversibility of heart failure. Whether cardiac progenitors exist in adult myocardium itself is unanswered, as is the question whether undifferentiated cardiac precursor cells merely fuse with preexisting myocytes. Here we report the existence of adult heart-derived cardiac progenitor cells expressing stem cell antigen-1. Initially, the cells express neither cardiac structural genes nor Nkx2.5 but differentiate in vitro in response to 5′-azacytidine, in part depending on Bmpr1a, a receptor for bone morphogenetic proteins. Given intravenously after ischemia/reperfusion, cardiac stem cell antigen 1 cells home to injured myocardium. By using a Cre/Lox donor/recipient pair (αMHC-Cre/R26R), differentiation was shown to occur roughly equally, with and without fusion to host cells.

Original languageEnglish (US)
Pages (from-to)12313-12318
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number21
DOIs
StatePublished - Oct 14 2003

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