Adult Hemangioblast/HSC Recruitment and Maintenance

成人成血管细胞/HSC 的招募和维持

• 批准号: 7095623
• 负责人: Edward W Scott
• 金额: $ 46.52万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-15 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7095623
• 关键词: CD34 molecule; RNA interference; Retroviridae; angiogenesis; bone marrow transplantation; bromodeoxyuridine; cell differentiation; cell migration; chemokine; electroporation; gene deletion mutation; genetically modified animals; hematopoietic stem cells; histology; laboratory mouse; magnetic resonance imaging; optical tomography; particle; phenotype; polymerase chain reaction; retina; selectins; tissue /cell culture; transfection /expression vector; vascular endothelium

DESCRIPTION (provided by applicant): We have proven that the adult hematopoietic stem cell (HSC) is able to function as a hemangioblast. Using a unique model of adult retinal neovascularization, we performed a series of experiments to ask if adult HSC exhibit hemangioblast activity by contributing to both blood and blood vessel repair in response to ischemic injury. Bone marrow transplant recipients were durably reconstituted with a single donor HSC from congenic mice expressing Gfp. Ischemia was induced in one retina per animal. Physiological localization of marrow-derived progeny to retina was detected by confocal microscopy of newly differentiated vascular tufts composed of Gfp+ endothelial cells. Both FACS and fluorescent microscopy confirmed full multilineage hematopoietic reconstitution of the transplant recipients. This study is the first to prove that an adult stem cell can exhibit functional plasticity in a transplant setting. In this proposal we seek to utilize this unique model to address the following hypotheses: Aim 1. Hypothesis: Remodeling of the endothelial niche by hemangioblast activity is the initial step in bone marrow remodeling following bone marrow transplant. Aim 2. Hypothesis: HSC hemangioblast activity produces a developmental hierarchy of cells with the potential to differentiate into endothelial cells. With our model we can define the lineage relationships and phenotypes of this new hematopoietic activity. Aim 3. Hypothesis: HSC are the source of circulating endothelial progenitors. Therefore, factors that affect HSC or leukocyte migration will affect EPC production and recruitment.

描述（由申请人提供）：我们已经证明，成年造血干细胞（HSC）能够充当血管细胞。使用成人视网膜新血管形成的独特模型，我们进行了一系列实验，以询问成年HSC是否通过响应缺血性损伤的血管和血管修复来促进血管细胞活性。骨髓移植受者与表达GFP的同类小鼠的单个供体HSC持久地重构。每只动物的一个视网膜诱导缺血。通过由GFP+内皮细胞组成的新分化的血管簇的共聚焦显微镜检测到骨髓来源对视网膜的生理定位。 FACS和荧光显微镜都证实了移植受者的全部多素造血重建。这项研究是第一个证明成年干细胞可以在移植环境中表现出功能可塑性的研究。在此提案中，我们试图利用这种独特的模型来解决以下假设：目标1。假设：通过血管细胞活性重塑内皮细胞生态位，是骨髓移植后骨髓重塑的第一步。 AIM 2。假设：HSC血管细胞活性产生细胞的发育层次结构，有可能分化为内皮细胞。通过我们的模型，我们可以定义这种新造血活性的谱系关系和表型。 AIM 3。假设：HSC是循环内皮祖细胞的来源。因此，影响HSC或白细胞迁移的因素会影响EPC的产生和募集。