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Recently, an therapeutic angiogenesis based on human adipose-derived stem cells (hASCs) in an ischemic model was reported. However, their low differentiation efficiency limits further application of ASCs in clinical therapy. We sought to develop an artificial ECM for hASCs differentiation and to demonstrate that hASCs cultured on FGF2- immobilized substrate were readily differentiated into vascular cells. hASCs formed three-dimensional cell masses (3DCM) on FGF-immobilized substrate and produced angiogenic factors, such as VEGF. Tubular microvessels were observed in the ischemic hind limb of rat as well as nude mice that received the 3DCMs transplant, and were recognized by antibodies against human-SMA, KDR, CD31, and CD34, but not by antibodies against murine antigens. These results suggest that the vasculatures were originated from the human cells. The ability of implanted cells to be directly incorporated into newly formed vasculature has been a matter of debate. Transplanted ASCs or ASC-derived endothelial lineage cells resulted in host angiogenesis via the secretion of pro-angiogenic factors, and were partially involved in the neovascularization in mice hind-limb ischemia. However, it was not reported whether the cells formed vascular networks in vivo. In our study, an efficient method to form mature vasculature from human ASCs was described. In our knowledge, this study is the first to demonstrate direct vasculature formation from adult stem cells.