Biologics of Adult Endothelial Progenitor Cells

成体内皮祖细胞的生物制剂

• 批准号: 7511102
• 负责人: Elmer M Price
• 金额: $ 21.19万
• 依托单位: MARSHALL UNIVERSITY
• 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 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7511102
• 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）：本修订版R21是对题为“定向干细胞分化用于心脏、肺和血液以及衰老疾病的细胞疗法”的PA的回应。该补助金的前提是，内皮功能障碍是与条件（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。血管修复部分由循环内皮祖干细胞（EPCs）的募集介导，该提案的中心主题是EPCs代表参与维持血管健康和预防疾病的循环胎儿后（成人）血管功能干细胞。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。这种知识是使用血管祖细胞合理开发基于细胞的疗法的绝对先决条件，这种方法具有治疗许多危及生命的疾病的巨大潜力。待检验的主要假设是原始EPCs和成熟内皮细胞在生物学上固有地不同，并且各自需要独特的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的可用性。目的1是采用新的细胞培养方法从成年动物外周循环中分离EPCs，建立增殖但未分化的细胞克隆系。目的2是使用独特的方法建立增殖的培养条件，包括悬浮培养和选择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。目的3是表征EPCs的功能和与分化状态相关的分子标志物，并确定使用细胞外基质和生长因子/细胞因子的组合诱导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，并将产生新的成人血管祖细胞系，用于最终开发基于细胞的血管生成或血管发生，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，这里描述的工作将导致这些疾病的新疗法。