Paracrine factors of vascular endothelial cells facilitate cardiomyocyte differentiation of mouse embryonic stem cells
Paracrine factors of vascular endothelial cells facilitate cardiomyocyte differentiation of mouse embryonic stem cells
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DOI：
10.1016/j.bbrc.2008.09.160
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发表时间：
2008-12-12
影响因子：
3.1
通讯作者：
Kodama, Itsuo
中科院分区：
文献类型：
--
作者：
Kado, Miwako;Lee, Jong-Kook;Kodama, Itsuo
对于心肌再生治疗来说，足以替代受损心肌组织的功能性心肌细胞的低分化能力是主要困难之一。利用Nkx2.5-GFP基因敲入ES细胞，我们展示了一种新的有效的方法，从胚胎干细胞（ES细胞）获得心肌细胞。当ES细胞与来自主动脉内皮细胞（ECs）的条件培养基一起培养时，GFP阳性细胞的比例显著增加，伴随着心脏特异性基因以及其他中胚层基因的上调。当在ES细胞分化培养的早期阶段（第0-3天）加入EC条件培养基时，促进作用更显著。骨形态发生蛋白（BMP）、环氧合酶（考克斯）和一氧化氮合成酶（NO）的抑制剂阻止了EC条件培养基对心肌形成的促进作用。这些结果表明，EC条件培养基的补充能够通过促进中胚层诱导而有效地获得心肌细胞，中胚层诱导由BMP、考克斯和NOS调节。(C)2008年爱思唯尔公司All rights reserved.
For myocardial regeneration therapy, the low differentiation capability of functional cardiomyocytes sufficient to replace the damaged myocardial tissue is one of the major difficulties. Using Nkx2.5-GFP knock-in ES cells, we show a new efficient method to obtain cardiomyocytes from embryonic stein (ES) cells. The proportion of GFP-positive cells was significantly increased when ES cells were Cultured with a conditioned medium from aortic endothelial cells (ECs), accompanied by upregulation of cardiac-specific genes as well as other mesodermal genes. The promotion was more prominent when EC-conditioned medium was added at an early stage of ES cell differentiation culture (Day 0-3). Inhibitors of bone morphogenic protein (BMP), cyclooxygenase (COX), and nitric oxide synthetase (NO) prevented the promotion of cardiomyogenesis by EC-conditioned medium. These results suggest that supplementation of EC-conditioned medium enables cardiomyocytes to be obtained efficiently through promotion of mesoderm induction, which is regulated by BMP, COX, and NOS. (C) 2008 Elsevier Inc. All rights reserved.