Cardiac Sca-1(+) Cells Are Not Intrinsic Stem Cells for Myocardial Development, Renewal, and Repair.
Cardiac Sca-1(+) Cells Are Not Intrinsic Stem Cells for Myocardial Development, Renewal, and Repair.
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心脏 Sca-1( ) 细胞不是心肌发育、更新和修复的内在干细胞。
DOI：
10.1161/circulationaha.118.035200
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发表时间：
2018
期刊：
影响因子：
37.8
通讯作者：
Cai Chen-Leng
中科院分区：
文献类型：
--
作者：
Zhang Lu;Sultana Nishat;Yan Jianyun;Yang Fan;Chen Fuxue;Chepurko Elena;Yang Feng-Chun;Du Qinghua;Zangi Lior;Xu Mingjiang;Bu Lei;Cai Chen-Leng
背景十多年来，小鼠心脏内的Sca-1+细胞被广泛认为是具有多能性的干细胞群，可以在体外和心脏移植后产生心肌细胞、内皮细胞和平滑肌细胞。然而，这些cells的发育起源和真实的性质仍然难以捉摸。MethodsHere，我们使用了一系列高保真遗传小鼠模型来表征心脏常驻Sca-1+cells.ResultsWith这些新的遗传工具，我们发现Sca-1不标记心脏前体细胞在早期胚胎心脏形成。出生后心脏驻留Sca-1+细胞实际上是一个纯内皮细胞群。他们保留内皮细胞的特性，并表现出最小的心肌潜力，在发展过程中，正常老化和缺血性injuries.ConclusionsOur研究提供了明确的见解，心脏常驻Sca-1+细胞的性质。这些观察结果挑战了目前的教条，即心脏驻留Sca-1+细胞是心肌发育，更新和修复的内在干细胞，并建议移植Sca-1+细胞在心脏修复中的机制需要重新评估。
BackgroundFor more than a decade, Sca-1+cells within the mouse heart have been widely recognized as a stem cell population with multipotency that can give rise to cardiomyocytes, endothelial cells, and smooth muscle cells in vitro and after cardiac grafting. However, the developmental origin and authentic nature of these cells remain elusive.MethodsHere, we used a series of high-fidelity genetic mouse models to characterize the identity and regenerative potential of cardiac resident Sca-1+cells.ResultsWith these novel genetic tools, we found that Sca-1 does not label cardiac precursor cells during early embryonic heart formation. Postnatal cardiac resident Sca-1+cells are in fact a pure endothelial cell population. They retain endothelial properties and exhibit minimal cardiomyogenic potential during development, normal aging and upon ischemic injury.ConclusionsOur study provides definitive insights into the nature of cardiac resident Sca-1+cells. The observations challenge the current dogma that cardiac resident Sca-1+cells are intrinsic stem cells for myocardial development, renewal, and repair, and suggest that the mechanisms of transplanted Sca-1+cells in heart repair need to be reassessed.