Role of BMP4 in hESC derived endothelial progenitors

BMP4 在 hESC 衍生的内皮祖细胞中的作用

• 批准号: 7058016
• 负责人: NOLAN Lee BOYD
• 金额: $ 4.88万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7058016
• 关键词: angiogenesis; bone morphogenetic proteins; cell differentiation; cell growth regulation; cell morphology; developmental genetics; gene expression; human embryonic stem cell line; mesoderm; postdoctoral investigator; protein structure function; tissue /cell culture

DESCRIPTION (provided by applicant): Human embryonic stem cells (hESC) can potentially be used as models of vascular development, angiogenesis, vascular pathogenesis, drug discovery and tissue engineering. Yet little is known about the mechanisms controlling hESC differentiation along the pathway toward the endothelial lineage. For example, bone morphogenic protein (BMP) 4, a potent mesoderm inducer, is known to play a role in vascular development in various animal models but it is unclear what role BMP4 plays in human vasculogenesis. Here we have developed a model of hESC differentiation based on embryoid bodies adhering to a Matrigel gel substrate in EGM-2 medium. After 7 days in culture we detected by RT-PCR significantly increased expression of endothelial markers (e.g. KDR, VE-Cad, PECAM1, CD34, eNOS, vWF, Tie-2). Our preliminary results indicate that a relatively simple hESC developmental vasculogenesis model may be used to study temporal gene expression therefore we propose to examine the role of BMP4 in the hESC differentiation and endothelial development. The NIH hESC registry codes for cell lines used in this research are:BG01,BG02 and WA09.

描述（由申请人提供）：人胚胎干细胞（hESC）可潜在地用作血管发育、血管生成、血管发病机制、药物发现和组织工程的模型。然而，人们对于控制 hESC 向内皮谱系分化的机制知之甚少。例如，骨形态发生蛋白 (BMP) 4 是一种有效的中胚层诱导剂，已知在各种动物模型的血管发育中发挥作用，但尚不清楚 BMP4 在人类血管发生中发挥什么作用。在这里，我们开发了一种 hESC 分化模型，该模型基于 EGM-2 培养基中粘附到基质胶凝胶基质上的拟胚体。培养 7 天后，我们通过 RT-PCR 检测到内皮标记物（例如 KDR、VE-Cad、PECAM1、CD34、eNOS、vWF、Tie-2）的表达显着增加。我们的初步结果表明，相对简单的 hESC 发育血管发生模型可用于研究时间基因表达，因此我们建议检查 BMP4 在 hESC 分化和内皮发育中的作用。本研究中使用的细胞系的 NIH hESC 注册代码为：BG01、BG02 和 WA09。