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Angiogenesis Induction by Vasculogenic Progenitor Cells

血管生成祖细胞诱导血管生成

基本信息

批准号：
7107253
负责人：
JOSEPH ITSKOVITZ-ELDOR
金额：
$ 28.44万
依托单位：
TECHNION-ISRAEL INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-09-01 至 2007-07-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Induction of new vascular growth in ischemic disorders of the coronary and peripheral vasculature is significant for its therapeutic implications. Vascularization in vivo could restore cellular viability, induce structural organization and promote integration upon implantation. Embryonic stem (ES) cells have the capability to differentiate and form blood vessels de novo in a process called vasculogenesis. We have shown experimental evidence for the existence of a common progenitor cell population of endothelial, smooth muscle and hematopoietic (ESH) cells, derived from human embryonic stem (hES) cells. Using a novel approach, we generated from hES lines H9 and H13 (NIH code WA13 and WA14 respectively) a proliferating cell population, which exhibits high levels of endothelial markers and up-regulation of early lineage markers of both endothelial and hematopoietic cells. We hypothesize that vascular progenitor cells can induce angiogenesis in ischemic tissues. For this research we will use the hES lines derived in our laboratory 13, 16 and J3 (NIH code TE03, TE06 and TE07) and H9 and H13 (NIH code WA09 and WA13) and their clones. Our initial focus will be to characterize and optimize the stability of vascular progenitor cells in vitro, and further amplify their growth and expansion to make them suitable for cell therapy implementation. A second goal will be to study human vasculogenesis using the hES cell system. We will study and enhance the natural mechanism of angiogenesis, in vitro, using time-lapse video records, then transfer angiogenic genes to hES cells. Finally we will study the effects of shear stress on hES cells and vascularize three dimensional polymeric scaffolds. Finally, we plan to examine the vascular progenitor cells in vivo. We expect that this research will establish the foundation for an effective therapeutic modality using hES cells for some of the most leading causes of morbidity and mortality in the world.

描述（由申请人提供）：诱导冠状动脉和外周血管系统缺血性疾病中的新血管生长对于其治疗意义是重要的。体内血管化可以恢复细胞活力，诱导结构组织并促进植入后的整合。胚胎干细胞（ES）具有在称为血管发生的过程中分化和从头形成血管的能力。我们已经显示了实验证据，证明存在一个共同的祖细胞群体的内皮细胞，平滑肌细胞和造血（ESH）细胞，来自人胚胎干细胞（hES）。使用一种新的方法，我们从hES系H9和H13（NIH代码分别为WA13和WA14）产生增殖细胞群，其表现出高水平的内皮标志物和内皮细胞和造血细胞的早期谱系标志物的上调。我们假设血管祖细胞可以诱导缺血组织中的血管生成。在本研究中，我们将使用我们实验室13、16和J3（NIH代码TE 03、TE 06和TE 07）以及H9和H13（NIH代码WA 09和WA 13）中衍生的hES系及其克隆。我们最初的重点将是表征和优化血管祖细胞在体外的稳定性，并进一步扩增它们的生长和扩增，使它们适合于细胞治疗的实施。第二个目标将是使用hES细胞系统研究人类血管发生。我们将在体外研究和增强血管生成的天然机制，利用延时录像记录，然后将血管生成基因转移到hES细胞中。最后，我们将研究剪切力对hES细胞和血管化三维聚合物支架的影响。最后，我们计划在体内检测血管祖细胞。我们希望这项研究将为使用hES细胞治疗世界上一些最主要的发病和死亡原因的有效治疗方式奠定基础。