Following changes in phenotype that occured over several BYL719 PI3K inhibitor passages revealed that CD73, CD166, PR-957 Proteasome inhibitor SSEA-4 and Sca-1 decreased with increased propagation, and grew in similarity to BMMSCs while the MHC I expression was still negative for EMSCs. In conclusion, our established EMSCs can be classified as mesenchymal stem cells and were distinct from BMMSCs. In principle, cellular aging can be accelerated with increased propagating and can affect amplified differentiation potential. Our results showed that cultured EMSCs showed less SAb- gal positive cells than BMMSCs over several passages. Cyclindependent kinase markers, p16 and p21, were important for terminal growth arrest, and EMSCs showed lower p16 and p21 expression than BMMSCs regardless of primary or longer passages. Due to the potentials of multilineage differentiation and low immunogenicity, MSCs draw attention for the use in regenerative medicine. Recent researches also demonstrated that some therapeutic effects of MSCs may derive from their paracrine effects. In our study, EMSCs not only showed great proliferation and differentiation potentials but also demonstrated immunosuppressive and anti-inflammation capacities through a paracrine effect. Thus, it is reasonable to expect that EMSCs are at least as potential as other MSCs for cell therapy. We evaluated the therapeutic effects of EMSCs in three animal models, including bone fracture, skin flap and hindlimb ischemia models. Our study showed that transplanted EMSCs accelerated the fracture healing process and enhanced osteocalcification indicating that EMSCs can promote fracture repair. It has been shown that MSCs contribute to angiogenesis directly by participating in new vessel formation, or indirectly by secreting angiogenic factors. Therefore, we used dorsal skin flap model, in which an oxygen tension gradient occurs in the ischemic tissue, to investigate the effects of EMSCs on the neovascularization in vivo. Transplanted EMSCs obviously reduced necrosis and almost fully protected the edge of the flap. In addition, EMSCs effectively preserved skin structures including the mucinous layer which is important for skin water content and tissue structural integrity. In hindlimb ischemia model, EMSCs improved blood perfusion and reduced muscle degeneration and tissue fibrosis. Moreover, EMSCs treatment significantly increased vWF positive capillary cells in both skin flap and hindlimb ischemia models, suggesting that EMSCs enhance neovascularization and might play a beneficial role in ischemic/hypoxia environment. Collectively, EMSCs were characterized as MSCs due to their capacities for differentiation into multiple lineages and cell surface marker expression profiles, while EMSCs were found to have greater abilities to proliferate and differentiate than BMMSCs.