Cardiac progenitor cells from adult myocardium: homing, differentiation, and fusion after infarction.
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 (alphaMHC-Cre/R26R), differentiation was shown to occur roughly equally, with and without fusion to host cells.
Oh
Hidemasa
H
Center for Cardiovascular Development, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Bradfute
Steven B
SB
Gallardo
Teresa D
TD
Nakamura
Teruya
T
Gaussin
Vinciane
V
Mishina
Yuji
Y
Pocius
Jennifer
J
Michael
Lloyd H
LH
Behringer
Richard R
RR
Garry
Daniel J
DJ
Entman
Mark L
ML
Schneider
Michael D
MD
D000818:Animals; D002454:Cell Differentiation; D002459:Cell Fusion; D002465:Cell Movement; D002469:Cell Separation; D015870:Gene Expression; D005796:Genes; D017930:Genes, Reporter; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D032386:Myoblasts, Cardiac / Q000378:metabolism / Q000473:pathology*; D009203:Myocardial Infarction / Q000235:genetics / Q000473:pathology*; D014157:Transcription Factors / Q000235:genetics
D014157:Transcription Factors