Angiogenesis Induction by Vasculogenic Progenitor Cells

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DESCRIPTION (provided by applicant): Induction of new vascular growth in ischemic disorders of the coronary and peripheral vasculature is significant for its therapeutic implications. Vascularization in vivo could restore cellular viability, induce structural organization and promote integration upon implantation. Embryonic stem (ES) cells have the capability to differentiate and form blood vessels de novo in a process called vasculogenesis. We have shown experimental evidence for the existence of a common progenitor cell population of endothelial, smooth muscle and hematopoietic (ESH) cells, derived from human embryonic stem (hES) cells. Using a novel approach, we generated from hES lines H9 and H13 (NIH code WA13 and WA14 respectively) a proliferating cell population, which exhibits high levels of endothelial markers and up-regulation of early lineage markers of both endothelial and hematopoietic cells. We hypothesize that vascular progenitor cells can induce angiogenesis in ischemic tissues. For this research we will use the hES lines derived in our laboratory 13, 16 and J3 (NIH code TE03, TE06 and TE07) and H9 and H13 (NIH code WA09 and WA13) and their clones. Our initial focus will be to characterize and optimize the stability of vascular progenitor cells in vitro, and further amplify their growth and expansion to make them suitable for cell therapy implementation. A second goal will be to study human vasculogenesis using the hES cell system. We will study and enhance the natural mechanism of angiogenesis, in vitro, using time-lapse video records, then transfer angiogenic genes to hES cells. Finally we will study the effects of shear stress on hES cells and vascularize three dimensional polymeric scaffolds. Finally, we plan to examine the vascular progenitor cells in vivo. We expect that this research will establish the foundation for an effective therapeutic modality using hES cells for some of the most leading causes of morbidity and mortality in the world.