Cardiac differentiation of embryonic stem cells by substrate immobilization of insulin-like growth factor binding protein 4 with elastin-like polypeptides
Cardiac differentiation of embryonic stem cells by substrate immobilization of insulin-like growth factor binding protein 4 with elastin-like polypeptides
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DOI：
10.1016/j.biomaterials.2011.09.070
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发表时间：
2012-01-01
期刊：
影响因子：
14
通讯作者：
Akaike, Toshihiro
中科院分区：
文献类型：
--
作者：
Minato, Ayaka;Ise, Hirohiko;Akaike, Toshihiro
胚胎干细胞（ESC）心肌细胞分化的建立是心血管再生医学的一个有用策略。在这里，我们报告了一种利用胰岛素样生长因子结合蛋白 4 (IGFBP4) 与弹性蛋白样多肽的基质固定化 ESC 心肌细胞分化的策略。最近，据报道 IGFBP4 通过抑制 Wnt/β-catenin 信号传导来促进 ESC 的心肌细胞分化。然而，需要大量的IGFBP4（约1μg/mL）来抑制Wnt/β-连环蛋白信号传导并诱导向心肌细胞的分化。我们在此报告了使用 IGFBP4 固定基质诱导心肌细胞分化。 IGFBP4 固定底物是通过与弹性蛋白样多肽融合而产生的。 IGFBP4 通过类弹性蛋白多肽的融合被稳定地固定在聚苯乙烯培养皿上。 IGFBP4 固定底物强烈且持续地抑制 Wnt/β-catenin 信号传导，有效促进 ESC 的心肌细胞分化。这些结果证明可以使用弹性蛋白样多肽的融合来固定IGFBP4。我们的结果还表明 IGFBP4 的底物固定是 ESC 分化为心肌细胞的有力工具。这些发现表明，可溶性因子的底物固定化是再生医学和组织工程中 ESC 分化的有用技术。 (C) 2011 Elsevier Ltd. 保留所有权利。
The establishment of cardiomyocyte differentiation of embryonic stem cells (ESCs) is a useful strategy for cardiovascular regenerative medicine. Here, we report a strategy for cardiomyocyte differentiation of ESCs using substrate immobilization of insulin-like growth factor binding protein 4 (IGFBP4) with elastin-like polypeptides. Recently, IGFBP4 was reported to promote cardiomyocyte differentiation of ESCs through inhibition of the Wnt/beta-catenin signaling. However, high amounts of IGFBP4 (approximately 1 mu g/mL) were required to inhibit the Wnt/beta-catenin signaling and induce differentiation to cardiomyocytes. We report herein induction of cardiomyocyte differentiation using IGFBP4-immobilized substrates. IGFBP4-immobilized substrates were created by fusion with elastin-like polypeptides. IGFBP4 was stably immobilized to polystyrene dishes through fusion of elastin-like polypeptides. Cardiomyocyte differentiation of ESCs was effectively promoted by strong and continuous inhibition of Wnt/beta-catenin signaling with IGFBP4-immobilized substrates. These results demonstrated that IGFBP4 could be immobilized using fusion of elastin-like polypeptides. Our results also demonstrate that substrate immobilization of IGFBP4 is a powerful tool for differentiation of ESCs into cardiomyocytes. These findings suggest that substrate immobilization of soluble factors is a useful technique for differentiation of ESCs in regenerative medicine and tissue engineering. (C) 2011 Elsevier Ltd. All rights reserved.