Cardiac progenitor cells from adult myocardium: Homing, differentiation, and fusion after infarction
Cardiac progenitor cells from adult myocardium: Homing, differentiation, and fusion after infarction
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DOI：
10.1073/pnas.2132126100
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发表时间：
2003-10-14
影响因子：
11.1
通讯作者：
Schneider, MD
中科院分区：
文献类型：
--
作者：
Oh, H;Bradfute, SB;Schneider, MD
通过细胞移植或动员内源性细胞进行潜在的修复在心脏病中具有特别的吸引力，心肌细胞增殖的微弱能力可能导致心力衰竭的不可逆性。成人心肌中是否存在心脏前体细胞，以及未分化的心脏前体细胞是否只是与先前存在的心肌细胞融合的问题，目前还没有答案。在这里，我们报告了表达干细胞抗原-1的成人心脏来源的心脏前体细胞的存在。最初，这些细胞既不表达心脏结构基因，也不表达NKX2.5，但在体外对5‘-氮胞苷的反应发生分化，部分依赖于骨形态发生蛋白的受体BMPR1A。在缺血/再灌流后静脉给药，心脏干细胞抗原1细胞归巢于受损心肌。通过使用Cre/Lox供体/受体对(AlphaMHC-Cre/R26R)，在与宿主细胞融合和不融合的情况下，分化的发生大致相同。
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.