Calcium signals induce liver stem cells to acquire a cardiac phenotype
Calcium signals induce liver stem cells to acquire a cardiac phenotype
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DOI：
10.4161/cc.6.13.4454
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发表时间：
2007-07-01
期刊：
影响因子：
4.3
通讯作者：
Malouf, Nadia N.
中科院分区：
文献类型：
--
作者：
Anderson, Page A. W.;Muller-Borer, Barbara J.;Malouf, Nadia N.
在美国，心力衰竭是导致早逝和残疾的主要原因。干细胞治疗在治疗心肌梗死和心力衰竭方面引起了极大的兴趣。一些组织特异性成体干细胞表现出可塑性，因为它们是多能的，对新的微环境提供的诱导信号做出反应，并获得新的微环境内源性细胞的表型。获得这种表型的机制尚不清楚。我们已经证明了肝脏来源的克隆性干细胞系WB F344在体内和体外都能分化为心肌细胞。利用新生儿心脏细胞和WB F344细胞的共培养模型，我们发现这两种细胞之间的胞浆通讯导致钙诱导的心脏转录因子的转录，并似乎迎来了心脏表型。功能缝隙连接和IP3受体似乎是这一过程所必需的。我们认为，干细胞移植到受损心脏中时，观察到的低频率分化为心肌细胞的部分原因是，它们无法与健康的心肌细胞建立起正常的细胞间通讯，也无法接收激活心脏基因程序所需的指示信号。
Heart failure is a major cause of premature death and disability in the United States. Stem cell therapy has attracted great interest for the treatment of myocardial infarction and heart failure. Some tissue - specific adult - derived stem cells demonstrate plasticity in that they are multipotent, react to inductive signals provided by a new micro - environment, and acquire the phenotype of cells endogenous to the new micro - environment. The mechanism through which this phenotype is acquired is unknown. We have demonstrated that a liver - derived clonal stem cell line, WB F344, differentiate into cardiomyocytes in vivo and in vitro. Using a coculture model of neonatal heart cells and WB F344 cells, we have found that cytosolic communication between the two cell types results in calcium - induced transcription of cardiac transcription factors and appears to usher in the cardiac phenotype. Functional gap junctions and IP3 receptors appear to be required for this process. We propose that the observed low frequency of stem cell differentiation into cardiomyocytes when transplanted into the injured heart is due, in part, to their inability to establish functioning intercellular communications with healthy cardiomyocytes and receive instructive signals needed to activate a cardiac gene program.