Identification of vascular progenitor cells from monkey ES cells and application for cell implantation therapy with search for novel vascular inducing factor

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ES cells with totipotency and self-renewal attract many investigators' attention as promising cell sources for regeneration medicine. We previously reported that Flk-1, one of VEGF receptors, -positive cells derived from mouse ES cells can be differentiated into endothelial cells and vascular smooth muscle cells (VSMC) to construct blood vessels in vitro and named them as "vascular progenitor cells (VPC)". In this research, to aim at clinical application of ES cells-derived VPC to vascular regeneration medicine, we identified VPC in monkey ES cells. Undifferentiated monkey ES cells express Flk-1, unlike mouse ES cells. Differentiation of Flk-1 cells on collagen IV-coated dishes with VEGF induced Flk-1 +, alkaline phosphatase - cells, which can be differentiated into endothelial cells ad VSMC to construct blood vessel structures. We also examined the usefulness of ES cells-derived VPC for implantation to regenerate blood vessels in vivo. Implanted VPC differentiated with VEGF and serum in tumor angiogenesis model effectively contributed to neoangiogenesis and significantly augmented local blood flow, which suggests potentials of therapeutic application of ES cells-derived VPC.