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

被引:1252
作者
Oh, H
Bradfute, SB
Gallardo, TD
Nakamura, T
Gaussin, V
Mishina, Y
Pocius, J
Michael, LH
Behringer, RR
Garry, DJ
Entman, ML
Schneider, MD [1 ]
机构
[1] Baylor Coll Med, Ctr Cardiovasc Dev, Houston, TX 77030 USA
[2] Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA
[3] Baylor Coll Med, Debakey Heart Ctr, Houston, TX 77030 USA
[4] Baylor Coll Med, Dept Med, Houston, TX 77030 USA
[5] Baylor Coll Med, Dept Immunol, Houston, TX 77030 USA
[6] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA
[7] Baylor Coll Med, Dept Physiol & Mol Biophys, Houston, TX 77030 USA
[8] Univ Texas, SW Med Ctr, Dept Med, Dallas, TX 75390 USA
[9] Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA
[10] NIEHS, Res Triangle Pk, NC 27709 USA
[11] Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA
关键词
D O I
10.1073/pnas.2132126100
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:12313 / 12318
页数:6
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