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

具有全能性和自我更新能力的胚胎干细胞作为有前途的再生医学细胞来源，受到了许多研究者的关注。我们曾报道，来源于小鼠ES细胞的VEGF受体之一Flk-1阳性细胞在体外可分化为内皮细胞和血管平滑肌细胞（VSMC），并将其命名为“血管祖细胞（vascular progenitor cells， VPC）”。本研究针对胚胎干细胞衍生的VPC在血管再生医学中的临床应用，我们在猴胚胎干细胞中鉴定了VPC。与小鼠胚胎干细胞不同，未分化的猴子胚胎干细胞表达Flk-1。VEGF诱导Flk-1 +、碱性磷酸酶-细胞在iv型胶原包被培养皿上分化，可分化为内皮细胞和VSMC，构建血管结构。我们还研究了胚胎干细胞衍生的VPC用于植入体内血管再生的有效性。在肿瘤血管生成模型中植入与VEGF和血清分化的VPC，可有效促进新生血管生成，显著增加局部血流量，提示ES细胞源性VPC具有治疗应用潜力。

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.