Background:Although stem cells have been regarded as a promising therapeutic option, the marginal therapeutic effects of stem cells are limitations that must be overcome for the development of effective cell therapy. This study sought to identify the angio-vasculogenic properties of endothelial differentiated mesenchymal stem cells (MSCs) and to determine whether these cells are effective for vascular repair.Methods and Results:Adipose MSCs were cultured for 10 days under endothelial cell (EC) culture conditions. These endothelial cell differentiated adipose MSCs (EA) and undifferentiated adipose MSCs (UA) were characterized via angiogenesis and adhesion assays. These cells were transplanted into a hindlimb ischemia (HLI) model to determine therapeutic effects and their underlying mechanisms. EA displayed low adhesion and angiogenic properties in vitro compared with UA. When implanted into mouse HLI models, EA exhibited the decreased recovery of blood perfusion in limb ischemia than uncultured UA. Histology data showed that injected EA exhibited lower retention, angiogenic cytokine levels, and neovascularization in vivo than did UA. Short-term differentiated EA display less cell engraftment and angio-vasculogenic potential, and are less effective for peripheral vascular repair than UA.Conclusions:EC differentiation of MSCs may not present an effective strategy for the promotion of therapeutic neovascularization.