Role of Adult Angioblasts in Vascular Maintenance

成体成血管细胞在血管维护中的作用

• 批准号: 7057402
• 负责人: GINA C SCHATTEMAN
• 金额: $ 24.49万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7057402
• 关键词: CD14 molecule; CD34 molecule; angiogenesis; cell differentiation; cell growth regulation; diabetes mellitus; enzyme linked immunosorbent assay; flow cytometry; genetically modified animals; green fluorescent proteins; hematopoiesis; hematopoietic stem cells; human tissue; ischemia; laboratory mouse; tissue /cell culture; vascular endothelium

DESCRIPTION (provided by applicant): Bone marrow derived stem cells are under intense study as potential therapeutic agents for a wide variety of pathologies. Treatment with exogenous bone marrow cells can improve myocardial function after infarct and brain function after stroke in rodents. Despite tremendous progress in the development of potential clinical uses of bone marrow stem cells, little is known about their normal in vivo functions or factors controlling their growth and differentiation. Further, nothing is known about the changes that occur in these cells once they move from the bone marrow to the blood, yet it is thought that the cells must travel through the blood to reach the site of tissue damage. Also, it has not been determined if circulating cells are equivalent to the multi-potent bone marrow stem cells, but preliminary data from our and other laboratories suggest that at a minimum, progenitors for many cell types reside in the blood. To begin to understand circulating stem cell biology we have focused on one type, namely circulating endothelial cell progenitors (CEPs), i.e, circulating cells that can differentiate into endothelial cells. Our first goal is to further the understanding of CEP biology by better delineating their phenotype(s) and identifying factors that control their growth and differentiation. This understanding may allow us to modulate CEP function in vivo to clinical advantage. Another component of stem cell biology about which little is known is how systemic disorders might alter their function. Our interest in particular is in how diabetes may affect CEP function. Evidence from our laboratory indicates that CEP dysfunction may be involved in diabetes associated vascular disease and that CEP therapy can improve vascularization in diabetic mice. Our second goal is to determine how the diabetic environment alters CEP function. To accomplish our goals we will 1) define the role of blood-derived CD34+ and CD14+ enriched cells in neovascularization in vivo; 2) identify molecular and cellular regulators of CEP growth and differentiation, and potential diabetes induced changes in these regulators in vivo; and 3) delineate potential roles of exogenous CEP modulators on CEP function in neovascularization in diabetic and non-diabetic mice.

描述（由申请人提供）：骨髓源性干细胞作为多种病理学的潜在治疗剂正在进行深入研究。外源性骨髓细胞治疗可以改善啮齿类动物梗死后的心肌功能和中风后的脑功能。尽管在开发骨髓干细胞的潜在临床用途方面取得了巨大进展，但对其正常的体内功能或控制其生长和分化的因素知之甚少。此外，我们对这些细胞从骨髓进入血液后发生的变化一无所知，但人们认为这些细胞必须穿过血液才能到达组织损伤部位。此外，还没有确定循环细胞是否等同于多能骨髓干细胞，但我们和其他实验室的初步数据表明，至少许多细胞类型的祖细胞存在于血液中。为了开始理解循环干细胞生物学，我们集中于一种类型，即循环内皮细胞祖细胞（CEP），即可以分化成内皮细胞的循环细胞。我们的第一个目标是通过更好地描述它们的表型和识别控制它们的生长和分化的因素来进一步理解CEP生物学。这种理解可能使我们能够在体内调节CEP功能以获得临床优势。干细胞生物学的另一个鲜为人知的组成部分是系统性疾病如何改变它们的功能。我们特别感兴趣的是糖尿病如何影响CEP功能。来自我们实验室的证据表明CEP功能障碍可能与糖尿病相关的血管疾病有关，并且CEP治疗可以改善糖尿病小鼠的血管形成。我们的第二个目标是确定糖尿病环境如何改变CEP功能。为了实现我们的目标，我们将1）确定血液来源的富含CD 34+和CD 14+的细胞在体内新血管形成中的作用; 2）鉴定CEP生长和分化的分子和细胞调节剂，以及体内这些调节剂中潜在的糖尿病诱导的变化;和3）描述外源性CEP调节剂对糖尿病和非糖尿病小鼠中新血管形成中CEP功能的潜在作用。