Biologics of Adult Endothelial Progenitor Cells

成体内皮祖细胞的生物制剂

• 批准号: 7195410
• 负责人: Elmer M Price
• 金额: --
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-15 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7195410
• 关键词: Adhesions; Adult; Age; Aging; Automobile Driving; Biochemical; Biological Markers; Biology; Blood; Blood Circulation; Blood Vessels; Cardiovascular Diseases; Cell Differentiation process; Cell Line; Cell Proliferation; Cell Therapy; Cells; Cellular biology; Cloning; Condition; Cultured Cells; Development; Diabetes Mellitus; Disease; Endothelial Cells; Environment; Etiology; Extracellular Matrix; Family suidae; Functional disorder; Gender; Goals; Grant; Green Fluorescent Proteins; Growth; Growth Factor; Health; Heart; Human; Hyperlipidemia; Hypertension; Impairment; Knowledge; Lead; Life; Lung; Mediating; Methods; NIH Program Announcements; Natural regeneration; Nature; Obesity; Peripheral Blood Stem Cell; Population; Production; Proliferating; Property; Recruitment Activity; Research; Source; Stem cells; Subgroup; Surface; Suspension Culture; Testing; Therapeutic; Thinking; Time; Transgenic Organisms; Undifferentiated; Vascular Diseases; Work; angiogenesis; base; cardiovascular disorder prevention; cytokine; design; fetal; fetal stem cell; field study; flasks; insight; interest; mature animal; neovascularization; novel; prevent; progenitor; repaired; response; vasculogenesis

DESCRIPTION (provided by applicant): This revised R21 is in response to the PA entitled "Directed Stem Cell Differentiation for Cell-Based Therapies for Heart, Lung, and Blood, and Aging Diseases". This grant is based on the premise that endothelial dysfunction underlies the pathophysiology of vascular impairment associated with conditions (hypertension, hyperlipidemia, obesity, aging) and diseases (diabetes, cardiovascular disease). Vascular repair is partially mediated by the recruitment of circulating endothelial progenitor stem cells (EPCs) and the central theme of this proposal is that EPCs represent circulating post-fetal (adult) vasopotent stem cells that are involved in maintaining vascular health and preventing disease. Our long-term goal is to develop EPC-based therapies for vascular disease and our specific aims will provide fundamental information regarding the biology of these cells. This knowledge is an absolute prerequisite for the rational development of cell- based therapies using vascular progenitor cells, an approach that holds tremendous potential for treating a host of life-threatening diseases. The main hypothesis to be tested is that primordial EPCs and mature endothelial cells are inherently biologically different and each requires a unique environmental milieu to control proliferation and differentiation. Our studies will exploit the availability of GFP transgenic swine as a source of cells. Aim 1 is to isolate EPCs from the peripheral circulation of adult animals employing novel cell culture methods to establish clonal lines of proliferating, but undifferentiated, cells. Aim 2 is to establish culture conditions for proliferation using unique methods, including suspension culture and selected growth factors and cytokines, to provide the environment for robust growth while suppressing differentiation. Aim 3 is to characterize EPCs in terms of function and molecular markers associated with differentiation state and to define the conditions that induce EPC differentiation into mature endothelial cells using combinations of extracellular matrices and growth factors/cytokines. This project will provide crucial insight into the mechanisms that control differentiation and will yield novel adult vascular progenitor cell lines for the eventual development of cell-based angiogenesis or vasculogenesis for reversing vascular disease. This work is highly relevant to human health. Heart and blood vessel disorders are major killers of people of all genders and ages and the work described here will lead to new treatments for these diseases.

描述（由申请人提供）：此修订版 R21 是对题为“针对心脏、肺、血液和衰老疾病的细胞疗法的定向干细胞分化”的 PA 的回应。该拨款的前提是内皮功能障碍是与病症（高血压、高脂血症、肥胖、衰老）和疾病（糖尿病、心血管疾病）相关的血管损伤的病理生理学基础。血管修复部分是由循环内皮祖干细胞 (EPC) 的募集介导的，该提案的中心主题是 EPC 代表循环的胎儿后（成人）血管强干细胞，参与维持血管健康和预防疾病。我们的长期目标是开发基于 EPC 的血管疾病疗法，我们的具体目标将提供有关这些细胞生物学的基本信息。这些知识是合理开发利用血管祖细胞的细胞疗法的绝对先决条件，这种方法在治疗许多危及生命的疾病方面具有巨大的潜力。要测试的主要假设是原始 EPC 和成熟内皮细胞在生物学上本质上是不同的，并且各自需要独特的环境环境来控制增殖和分化。我们的研究将利用 GFP 转基因猪作为细胞来源。目标 1 是采用新型细胞培养方法从成年动物的外周循环中分离 EPC，以建立增殖但未分化细胞的克隆系。目标 2 是使用独特的方法建立增殖培养条件，包括悬浮培养和选定的生长因子和细胞因子，以提供稳健生长的环境，同时抑制分化。目标 3 是在与分化状态相关的功能和分子标记方面表征 EPC，并使用细胞外基质和生长因子/细胞因子的组合来定义诱导 EPC 分化为成熟内皮细胞的条件。该项目将为控制分化的机制提供重要的见解，并将产生新的成体血管祖细胞系，用于最终发展基于细胞的血管生成或血管生成以逆转血管疾病。这项工作与人类健康密切相关。心脏和血管疾病是所有性别和年龄的人的主要杀手，这里描述的工作将为这些疾病带来新的治疗方法。