3: MECHANISMS OF DE NOVO HUMAN BLOOD VESSEL FORMATION

3：人类血管从头形成的机制

• 批准号: 8360264
• 负责人: ZACK Z. WANG
• 金额: $ 23.96万
• 依托单位: MAINEHEALTH
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8360264
• 关键词: Blood Vessels; CD34 gene; Cell Differentiation process; Cell Line; Cells; Centers of Research Excellence; Development; Embryo; Endothelial Cells; Fibroblasts; Funding; Future; Generations; Grant; Heart Valves; Human; Injury; Ischemia; Mesenchymal; Mus; National Center for Research Resources; Pericytes; Principal Investigator; Recruitment Activity; Regenerative Medicine; Research; Research Infrastructure; Resources; Serum; Smooth Muscle Myocytes; Source; Stem cells; System; Tissue Engineering; United States National Institutes of Health; cost; human embryonic stem cell; human embryonic stem cell line; in vivo; novel therapeutics; stem cell biology

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. After initial establishment of an endothelial network in vivo, the surrounding mesenchymal cells differentiate into mural cells, including smooth muscle cells (SMC) or pericytes, and are recruited to support the vascular network by stabilizing nascent endothelial vessels during mouse vascular development. However, it is unclear how human mesenchymal cells and SMC facilitate de novo human blood vessel formation and maturation. We recently found that mouse 10T1/2 cells (mouse embryonic fibroblast cell line with mesenchymal potential) enhanced human embryonic stem cell (hESC)-derived blood vessel formation in vivo. To understand the interactive relationship of endothelial cells (EC) and SMC during vascular development, we established an effective hESC system for the generation of CD34+ progenitor cells. Our preliminary studies show that CD34+ cells derived from hESCs have potential to become endothelial cells (EC) and SMCs. We propose the following Specific Aims: 1. To establish serum-free conditions and investigate factors that direct hESC generating EC and SMC from hESC. 2. To characterize vascular endothelial and SMC differentiation potential of CD34+ cells from hESCs. 3. To investigate the functions of human mural cells in supporting blood vessel development from hESCs. Our findings will have important implications for the possible future use of hESC in the tissue engineering of blood vessels for diseased human heart valves, and will provide a novel therapeutic option for ischemia or endothelial injury. Four NIH recent approved hESC lines, HUES 10, HUES 11, HUES 16, HUES 17 (NIHhESC-09-0023, 0024, 0029 and 0030) will be used.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的首席研究员可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 体内内皮网络初步建立后，周围的间充质细胞分化为壁细胞，包括平滑肌细胞（SMC）或周细胞，并在小鼠血管发育过程中通过稳定新生内皮血管而被招募来支持血管网络。然而，目前尚不清楚人类间充质细胞和SMC如何促进人类血管从头形成和成熟。我们最近发现小鼠 10T1/2 细胞（具有间充质潜能的小鼠胚胎成纤维细胞系）增强了体内人胚胎干细胞 (hESC) 来源的血管形成。为了了解血管发育过程中内皮细胞 (EC) 和 SMC 的相互作用关系，我们建立了有效的 hESC 系统来产生 CD34+ 祖细胞。我们的初步研究表明，源自 hESC 的 CD34+ 细胞有潜力成为内皮细胞 (EC) 和 SMC。我们提出以下具体目标： 1.建立无血清条件并研究指导hESC从hESC产生EC和SMC的因素。 2. 表征来自 hESC 的 CD34+ 细胞的血管内皮和 SMC 分化潜力。 3. 研究人壁细胞在支持hESC血管发育中的功能。 我们的研究结果将对 hESC 未来在患病人类心脏瓣膜血管组织工程中的应用产生重要影响，并将为缺血或内皮损伤提供一种新的治疗选择。将使用 NIH 最近批准的四个 hESC 系：HUES 10、HUES 11、HUES 16、HUES 17（NIHhESC-09-0023、0024、0029 和 0030）。