ADULT ANGIOBLASTS AND VASCULAR MAINTENANCE

成人成血管细胞和血管维护

• 批准号: 6177643
• 负责人: GINA C SCHATTEMAN
• 金额: $ 16.13万
• 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 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6177643
• 关键词: CD34 molecule; SCID mouse; angiogenesis; biomarker; cell adhesion; cell adhesion molecules; cell differentiation; cell growth regulation; cell proliferation; diabetes mellitus; diabetic angiopathy; diabetic retinopathy; flow cytometry; hematopoiesis; hematopoietic growth factor; hematopoietic stem cells; human tissue; hyperglycemia; hyperinsulinism; laboratory mouse; surface antigens; tissue /cell culture; vascular endothelium

The goal of this study is to further the understanding of the fundamental biology of adult angioblasts and to use this knowledge to test therapeutic strategies in the treatment of peripheral vascular disease. Peripheral vascular disease, stroke, diabetes, burns, and severe trauma are all characterized by impaired circulation. Conventional drug therapies to restore circulation have been only modestly successful, and it is to too soon to determine the extent of clinical gene therapy trials. Interestingly, the use of exogenous endothelial cells to augment new blood vessel growth is relatively untested. Recently it was found that peripheral blood contains cells that can differentiate into endothelial cells in vitro, incorporate into new blood vessels in vivo, and persist in the mouse for at least 6wk. This work is a first step in determining if these putative circulating endothelial cell precursors, called angioblasts, can be used to augment new blood vessel growth clinically. The long-term goal is to develop a procedure in which cells with embryonic-like differentiation capabilities can be retrieved from a patient, proliferated ex vivo, and returned to the patient, such that each patient becomes their own endothelial cell donor. In this study, angioblasts will be isolated in large numbers and factors that control their growth and differentiation will be investigated. Means to facilitate their use to enhance blood vessel growth in an ischemic limb model in both non-diabetic and diabetic mice will be developed. Because diabetes profoundly exacerbates macro- and microvascular disease, use of diabetic mice will provide a more stringent test of angioblast potential than would normal mice. We will also investigate the involvement of angioblasts in retinal vascularization to assess the possibility that anti-angioblast therapy may be an effective means of inhibiting proliferative retinopathy.

本研究的目的是加深对 成体成血管细胞的基础生物学，并利用这些知识 测试周围血管治疗的治疗策略 疾病。 周围血管疾病、中风、糖尿病、烧伤等 严重创伤的特点都是血液循环受损。 恢复循环的传统药物疗法仅 取得了一定的成功，现在判断其成功程度还为时过早 临床基因治疗试验。有趣的是，使用外源 内皮细胞促进新血管生长的作用相对较强 未经测试。 最近发现外周血中含有细胞 可以在体外分化为内皮细胞，并融入 体内新生血管，并在小鼠体内持续至少 6 周。 这项工作是确定这些假定的流通是否存在的第一步 内皮细胞前体，称为成血管细胞，可用于增强 临床上新血管生长。 长期目标是发展 具有胚胎样分化能力的细胞的过程 可以从患者身上检索能力，离体增殖，并且 返回给患者，让每个患者成为自己的患者 内皮细胞供体。 在这项研究中，将大量分离成血管细胞和因素 将研究控制其生长和分化的因素。 促进其使用以增强血管生长的方法 非糖尿病和糖尿病小鼠的缺血性肢体模型 发达。 因为糖尿病会严重加剧宏观和 微血管疾病，使用糖尿病小鼠将提供更多 比正常小鼠更严格的成血管细胞潜力测试。 我们将 还研究了视网膜中成血管细胞的参与 血管化以评估抗成血管细胞治疗的可能性 可能是抑制增殖性视网膜病变的有效手段。