The discovery that pluripotent cells reside in the stromal cell fraction of subcutaneous adipose tissue has revealed a novel source of cells for autologous cell therapy. These adipose stromal cells (ASCs) have been shown to differentiate into myocytes, chondrocytes and neural cells; however, little is known about their ability to differentiate into cells of vascular and hematopoietic lineages. Our preliminary data suggests that many human and murine ASCs express surface markers that are typically found on either hematopoietic or endothelial stem and progenitor cells. We will therefore attempt to clarify whether ASCs have the multipotentiality of incorporating into nascent or reparative vasculature in the context of ischemic angiogenesis or atherosclerotic intimal formation; and to contribute to hematopoiesis as well as circulating vascular progenitors following bone marrow ablation. We will also determine the particular markers that are associated with these potentials.
Specific Aim 1 will examine whether ASCs can differentiate into endothelial and vascular smooth muscle cells in vitro, enhance angiogenesis in vivo, and incorporate into the nascent vascular network in the setting of ischemia.
Specific Aim 2 will investigate whether ASCs have the potential to differentiate into hematopoietic cell lineages in vitro, and engraft into bone marrow as either hematopoietic stem cells or hemangioblasts, which can subsequently give rise to blood lineages as well as circulating vascular progenitors.
Specific Aim 3 will determine whether ASCs are capable of homing to sites of vascular injury, and modulating the local injury response, perhaps by providing endothelial cells or supporting those which pre-exist. Together, these studies will help define the multipotency and biology of ASCs, and delineate how ASCs could be used for autologous cell therapy in the setting of either cardiovascular or hematologic disease. ? ?
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