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

H Oh, SB Bradfute, TD Gallardo… - Proceedings of the …, 2003 - National Acad Sciences
H Oh, SB Bradfute, TD Gallardo, T Nakamura, V Gaussin, Y Mishina, J Pocius, LH Michael…
Proceedings of the National Academy of Sciences, 2003National Acad Sciences
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 …
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.
National Acad Sciences