A novel method to inhibit apoptosis and promote differentiation of induced pluripotent stem cells in transplantation therapy for myocardial infarction
A novel method to inhibit apoptosis and promote differentiation of induced pluripotent stem cells in transplantation therapy for myocardial infarction
复制标题
心肌梗死移植治疗中抑制诱导多能干细胞凋亡并促进分化的新方法
DOI：
10.1016/j.mehy.2010.10.016
复制
发表时间：
2011-02-01
影响因子：
4.7
通讯作者：
Zhang, Huimin
中科院分区：
文献类型：
--
作者：
Li, Jie;Han, Yaling;Zhang, Huimin
心肌缺血性疾病是世界范围内死亡的主要原因，目前的治疗只能延缓这些疾病的进展。传统的干细胞疗法在临床应用中面临着各种障碍，包括典型的伦理学和免疫学问题。近年来，诱导多能干细胞（iPS）被证明是一种新的、具有患者特异性和疾病特异性的多能干细胞的来源，而且不受体细胞核移植技术和伦理学的限制。然而，iPS细胞在梗死微环境中移植后的有限存活力以及向心血管组织的低分化率限制了它们的再生能力。基因修饰的iPS细胞与最近发现的细胞阻遏物的E1 A刺激的基因（CREG），抑制细胞凋亡和炎症，但增强分化，可能会解决这些关键问题。可能的机制包括CREG通过VEGF促进血管生成，通过激活PI 3 K/Akt和阻断p38 MARK信号传导抑制炎症和抗凋亡，以及维持内皮分化条件。CREG调控iPS细胞存活和分化的确切机制仍有待进一步研究。(C)2010年由Elsevier Ltd.出版
Myocardial ischemic disorders are the leading causes of mortality worldwide, and current therapies only delay progression of these diseases. Traditional stem cell therapies face various impediments, including the typical ethical and immunological problems in clinical application. Recently, induced pluripotent stem (iPS) cells have been shown to offer a novel fascinating route to patient-specific and disease-specific pluripotent cells, without the technical and ethical limitations of somatic cell nuclear transfer method. However, iPS cells' limited viability after transplantation in infarcted microenvironment, and low rate of differentiation into cardiovascular tissues restricts their regenerative capacity. Genetically modified iPS cells with the recently discovered cellular repressor of El A-stimulated genes (CREG), which inhibits apoptosis and inflammation but enhances differentiation, may resolve these crucial problems. Possible mechanisms may include CREG promotion of angiogenesis by VEGF, suppression of inflammation and resistance of apoptosis via activating PI3K/Akt and blocking p38 MARK signaling, and maintenance of endothelial differentiation conditions. The exact mechanisms that CREG can modulate iPS cells' survival and differentiation remain to be investigated. (C) 2010 Published by Elsevier Ltd.