Skeletal Muscle Stem Cells Become Vascular Cells In Vivo

提出的研究假设是，成体干细胞可以在体内诱导分化为血管细胞表型，并在体内提供必要的可溶性效应子和转录因子。我们以前的特点是多能骨髓干细胞的能力，产生内皮细胞（EC）和平滑肌细胞（SMC）使用小鼠模型的新血管形成。来自同一模型的进一步初步数据表明，来自小鼠骨骼肌的干细胞具有类似的分化成EC的能力。本研究的目的是：（1）。表征成血管细胞和血管特异性基因在源自成人骨骼肌的干细胞中的表达; II）。确定来源于成人骨骼肌的干细胞是否可以在体内分化为EC和SMC细胞; III）。促进成人骨骼肌干细胞同质群（SP）在体外分化为EC和SMC细胞。更好地了解成人骨骼肌干细胞的血管细胞分化过程中所涉及的机制，将使其在临床上重要的条件下有效分化。我们希望利用这些细胞来开发自体血管移植物，并增强人类患者缺血组织的修复。这些操作的干细胞也可以同样用作载体，用于将治疗目的基因递送到新形成的血管，用于心血管疾病、各种糖尿病并发症和肿瘤治疗。

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.