ADULT ANGIOBLASTS AND VASCULAR MAINTENANCE

本研究的目的是进一步了解 成人成血管细胞的基础生物学，并利用这些知识， 测试治疗外周血管疾病的治疗策略 疾病 外周血管疾病、中风、糖尿病、烧伤， 严重的创伤都以循环受损为特征。 恢复血液循环的传统药物疗法 这是一个成功的例子，现在还为时过早，以确定它的程度。 临床基因治疗试验有意思的是， 内皮细胞增加新血管生长是相对 未经测试 最近发现外周血中含有细胞 可以在体外分化成内皮细胞， 新血管在体内，并持续在小鼠至少6wk。 这项工作是确定这些假定的循环是否 内皮细胞前体，称为成血管细胞，可用于增加 临床上新血管生长。 长期目标是发展 一种将具有胚胎样分化的细胞 能力可以从患者体内获得，离体增殖， 回到病人身上，每个病人都变成了自己的。 内皮细胞供体。 在这项研究中，成血管细胞将被大量分离， 控制它们生长和分化的基因。 促进其用于增强血管生长的方法， 在非糖尿病和糖尿病小鼠中缺血肢体模型将 开发 因为糖尿病会严重加剧 微血管疾病，使用糖尿病小鼠将提供更多的 成血管细胞潜能的严格测试。 我们将 还研究了成血管细胞在视网膜病变中的参与。 评估抗成血管细胞治疗 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.