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.

F32HL068482

2001-08-01

1900-01-01