Cardiac muscle plasticity in adult and embryo by heart-derived progenitor cells
Cardiac muscle plasticity in adult and embryo by heart-derived progenitor cells
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DOI：
10.1196/annals.1302.015
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发表时间：
2004-01-01
期刊：
影响因子：
--
通讯作者：
Schneider, MD
中科院分区：
文献类型：
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作者：
Oh, H;Chi, X;Schneider, MD
损伤心脏中有心肌细胞增殖的证据提示，心脏再生可能是由心肌干细胞内或外源细胞发生的。然而，这些细胞的规格和来源仍不清楚。在这里，我们使用荧光激活的细胞分选方法报道，心脏前体细胞存在于成人心脏中，并与微小的毛细血管共存，位于表达高端粒酶活性的干细胞抗原(SCA-1)群体中。值得注意的是，在心脏来源的细胞中也发现了能够排出Hoechst 33342的造血干细胞，称为侧群细胞。心脏前体细胞(CD45(-)/CD34(-))在未分化阶段既不表达心肌标志物，也不表达内皮细胞标志物。暴露于5-氮胞苷可诱导心脏分化，这在一定程度上依赖于BMPR1A型骨形态发生蛋白(BMP)受体。通过胚泡注射证实了成年Sca1(+)细胞在胚胎发育中采用心肌的能力，使用来自转基因小鼠成年心脏的祖细胞，转基因小鼠携带通过Nkx-2.5基因位点表达GFP的细菌人工染色体。在缺血/再灌注后不久，静脉注射前体细胞，在宿主心肌中归巢并功能分化为左心室总体积的3.5%。Cre/loxP供体/受体系统证明，分化既包括融合非依赖成分，也包括融合相关成分。我们的研究表明，内源性心脏祖细胞存在于成人心脏中，在功能上再生心肌细胞，并整合到现有的心脏回路中。
The evidence of cardiomyocyte proliferation in damaged heart implied cardiac regeneration might occur by resident or extra cardiac stem cells. However, the specification and origin of these cells remain unknown. Here, we report using fluorescence-activated cell sorting that cardiac progenitor cells resided in adult heart and colocalized with small capillary vessels, within the stem cell antigen (Sca-1) population expressing high telomerase activity. Notably, hematopoietic stem cells capable of efflux Hoechst 33342, termed side-population cells, also were identified within the heart-derived cells. The cardiac progenitor cells (CD45(-)/CD34(-)) express neither cardiac muscle nor endothelial cell markers at an undifferentiated stage. The exposure of 5-azacytidine induced cardiac differentiation, which depends, in part, on Bmpr1a, a type IA receptor for bone morphogenetic protein (BMP). The capability of adult Sca1(+) cells to adopt a cardiac muscle in embryogenesis was substantiated by blastocyst injection, using progenitors from the adult hearts of transgenic mice that harbor a bacterial artificial chromosome expressing GFP via the Nkx-2.5 locus. Intravenously injected progenitors, shortly after ischemic/reperfusion, homed and functionally differentiated 3.5% of total left ventricle in the host myocardium. Differentiation included both fusion-independent and fusion-associated components, proved by the Cre/loxP donor/recipient system. Our studies suggest that endogenous cardiac progenitors reside in the adult heart, regenerate cardiomyocytes functionally, and integrate into the existing heart circuitry.