Skeletal Muscle Stem Cells Become Vascular Cells In Vivo

提出的研究假设是，在体内，只要提供必要的可溶性效应物和转录因子，就可以诱导成体干细胞分化为血管细胞表型。我们之前已经利用小鼠新生血管模型描述了多电位骨髓干细胞产生内皮细胞（EC）和平滑肌细胞（SMC）的能力。来自同一模型的进一步初步数据表明，来源于小鼠骨骼肌的干细胞具有类似的分化为EC的能力。本研究的目的是：1)。表征成人骨骼肌干细胞成血管细胞和血管特异性基因的表达；(二)。目的：观察成人骨骼肌干细胞能否在体内分化为EC细胞和SMC细胞；III)。目的促进成人骨骼肌干细胞同质群（SP）在体外向EC和SMC细胞分化。更好地了解血管细胞从成人骨骼肌干细胞分化过程的机制将使其在临床重要条件下有效分化。我们希望将这些细胞用于自体血管移植的发展，并增强人类患者缺血组织的修复。这些被操纵的干细胞也同样可以作为载体，为心血管疾病、各种糖尿病并发症和肿瘤治疗的新形成血管输送治疗性基因。

The hypothesis of the proposed studies is that adult stem cells can be induced to differentiate into vascular cell phenotypes in vivo and, upon provision of necessary soluble effectors and transcription factors in vivo. We have previously characterized the ability of multipotential bone marrow stem cells to give rise to endothelium (EC) and smooth muscle cells (SMC) using a murine model of neovascularization. Further preliminary data from the same model demonstrate that stem cells derived from murine skeletal muscle have a similar ability to differentiate into EC. The aims of this study are: I). To characterize the expression of angioblast and vascular specific genes in stem cells derived from adult skeletal muscle; II). To determine if stem cells derived from adult skeletal muscle can differentiate into EC and SMC cells in vivo; III). To promote differentiation of a homogeneous population (SP) of stem cells derived from adult skeletal muscle into EC and SMC cells in vitro. A better understanding of the mechanisms involved in the differentiation processes of vascular cells from adult skeletal muscle stem cells will enable their effective differentiation in clinically important conditions. We hope to use such cells for the development of autologous vessel grafts and to enhance repair of ischemic tissues in human patients. These manipulated stem cells may also be equally useful as vectors for delivering genes of therapeutic interest to newly forming blood vessels for cardiovascular disease, various diabetic complications and tumor treatment.