3: MECHANISMS OF DE NOVO HUMAN BLOOD VESSEL FORMATION

3：人类血管从头形成的机制

• 批准号: 7960394
• 负责人: ZACK Z. WANG
• 金额: $ 21.67万
• 依托单位: MAINEHEALTH
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7960394
• 关键词: Blood Vessels; CD34 gene; Cell Differentiation process; Cell Line; Cells; Centers of Research Excellence; Computer Retrieval of Information on Scientific Projects Database; Development; Embryo; Endothelial Cells; Fibroblasts; Funding; Future; Generations; Grant; Heart Valves; Human; Injury; Institution; Ischemia; Mesenchymal; Mus; Pericytes; Recruitment Activity; Regenerative Medicine; Research; Research Personnel; Resources; Serum; Smooth Muscle Myocytes; Source; Stem cells; System; Tissue Engineering; United States National Institutes of Health; WA01 cell line; WA09 Cell Line; 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. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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. NIH approved human embryonic stem cell lines H1 and H9 (WA01 and WA09) will be used.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 在体内建立了内皮网络后，周围的间充质细胞分化为包括平滑肌细胞（SMC）或周细胞的壁细胞，并通过在小鼠血管发育过程中稳定新生的内皮血管来招募来支持血管网络。但是，尚不清楚人类间充质细胞和SMC如何促进从头开始的人血管形成和成熟。我们最近发现，小鼠10T1/2细胞（具有间质电位的小鼠胚胎成纤维细胞系）增强了体内人类胚胎干细胞（HESC）衍生的血管形成。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，我们建立了一种有效的hESC系统，用于生成CD34+祖细胞。我们的初步研究表明，源自hESC的CD34+细胞具有成为内皮细胞（EC）和SMC的潜力。我们提出以下具体目标： 1。建立无血清条件并研究直接从hESC产生EC和SMC的因素。 2。表征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的血管发育中的功能。 我们的发现将对hESC在血管的组织工程中可能使用的人体心脏瓣膜的组织工程可能具有重要意义，并将为缺血或内皮损伤提供一种新颖的治疗选择。将使用NIH认可的人类胚胎干细胞系H1和H9（WA01和WA09）。