Human cardiac stem cells exhibit mesenchymal features and are maintained through Akt/GSK-3β signaling
Human cardiac stem cells exhibit mesenchymal features and are maintained through Akt/GSK-3β signaling
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DOI：
10.1016/j.bbrc.2006.11.096
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发表时间：
2007-01-19
影响因子：
3.1
通讯作者：
Oh, Hidemasa
中科院分区：
文献类型：
--
作者：
Tateishi, Kento;Ashihara, Eishi;Oh, Hidemasa
最近的证据表明，人类心脏干细胞（hCSCs）可能有心脏修复的临床应用，但其特性和其生长的调控机制尚未得到充分的研究。在这里，我们展示了hCSC在人类心脏中的起源和组织分布方面的新特性，并展示了调节其生长和存活的信号通路。端粒酶活性hCSC主要存在于右心房和心脏流出道（婴儿>成人），并具有间充质细胞样表型。这些hCSCs表达胚胎干细胞标志物，并在移植到缺血心肌时分化为心肌细胞以支持心脏功能。抑制Akt途径会损害hCSC的增殖并诱导细胞凋亡，而抑制糖原合成酶激酶-3（GSK-3）则会增强其生长和存活。我们的结论是，hCSC表现出间充质特征，Akt/GSK-3 β可能是人类心脏中hCSC维持的关键调节剂。(c)2006年爱思唯尔公司All rights reserved.
Recent evidence suggested that human cardiac stem cells (hCSCs) may have the clinical application for cardiac repair; however, their characteristics and the regulatory mechanisms of their growth have not been fully investigated. Here, we show the novel property of hCSCs with respect to their origin and tissue distribution in human heart, and demonstrate the signaling pathway that regulates their growth and survival. Telomerase-active hCSCs were predominantly present in the right atrium and outflow tract of the heart (infant > adult) and had a mesenchymal cell-like phenotype. These hCSCs expressed the embryonic stem cell markers and differentiated into cardio-myocytes to support cardiac function when transplanted them into ischemic myocardium. Inhibition of Akt pathway impaired the hCSC proliferation and induced apoptosis, whereas inhibition of glycogen synthase kinase-3 (GSK-3) enhanced their growth and survival. We conclude that hCSCs exhibit mesenchymal features and that Akt/GSK-3 beta may be crucial modulators for hCSC maintenance in human heart. (c) 2006 Elsevier Inc. All rights reserved.