Cell therapy using cells capable of generating or repairing functional blood vessels has the potential to treat a wide variety of disorders including acute and chronic myocardial ischemia, peripheral limb ischemia, and to effect local and systemic repair of atherosclerotic vessels However, as with many forms of cell therapy, one of the limiting factors is the availability of an accessible source of autologous cells capable of providing benefit. We have found that human adipose tissue contains cells with properties that suggest potential value in autologous vascular cell therapy. However, the identity and mechanism of action of these cells remains unclear. Further, it has been shown that cells with vascular potential derived from other tissue, such as blood or marrow, frequently exhibit impaired number and/or function in persons with risk factors for vascular disease. In these studies described in this Phase I proposal we will perform cell sorting and functional studies to identify the population or populations within adipose tissue that possess properties consistent with potential in vascular cell therapy. These studies will include evaluation of cells similar to EPCs that are capable of participating directly in repair and regeneration of the endothelium. However, while endothelialization and capillary growth and regeneration are important and valuable, many clinical problems need a more robust response that includes remodeling and expansion of larger vessels, a process that requires a complex interplay of multiple cell types and growth factors. Thus, we will also evaluate adipose tissue-derived cells with the potential act as mural cells and mural cell precursors. Finally, we will evaluate the number and function of adipose tissue-derived cells with vascular potential obtained from persons with risk factors for vascular disease including a history of smoking, hypertension, and diabetes. ? ? In this way we will provide the groundwork for Phase II studies that will evaluate mechanism of action of these populations in more detail and develop methods by which these cells can be harvested and delivered in a therapeutically effective fashion. ? ? ?
