ADULT ANGIOBLASTS AND VASCULAR MAINTENANCE

这项研究的目的是为了加深对 成人血管母细胞的基础生物学，并利用这一知识 测试治疗策略在周围血管治疗中的应用 疾病。外周血管疾病、中风、糖尿病、烧伤和 严重创伤的特点都是血液循环障碍。 恢复血液循环的传统药物疗法只是 取得了一定的成功，现在就确定 临床基因治疗试验。有趣的是，外源基因的使用 内皮细胞促进新生血管的生长相对来说 未经测试。最近发现，外周血中含有细胞 在体外可以分化为内皮细胞，并整合到 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循环是否 内皮细胞前体，称为血管母细胞，可用于增强 临床表现为新生血管生长。我们的长远目标是发展 具有胚胎样分化的细胞的过程 能力可以从患者身上恢复，体外增殖，以及 返回给病人，这样每个病人都成为他们自己的人 内皮细胞供体。 在这项研究中，将大量分离血管母细胞和因子 控制它们生长和分化的因素将被调查。 促进它们的使用以促进血管生长的手段 非糖尿病小鼠和糖尿病小鼠的肢体缺血模型 发展起来的。因为糖尿病深刻地加剧了宏观和 微血管病变时，使用糖尿病小鼠会提供更多 比正常小鼠更严格的血管母细胞潜能测试。我们会 同时研究视网膜中血管母细胞的参与情况。 血管化术评估抗血管母细胞治疗的可能性 可能是抑制增殖性视网膜病变的有效手段。

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.