Human umbilical cord-derived mesenchymal stem cells(hUCMSCs)isolated from human umbilical Whartons Jelly are a population of primitive and pluripotent cells．In different specific conditions，they can differentiate into different cells，such as adipocytes，osteoblasts，chondrocytes，neurocytes，endothelial cells etc．However,few reports on differentiating hUCMSCs into epidermal cells in vitro were published.There are several methods of MSCs differentiation for choice，such as the specific induction medium，direct or indirect co-culture. In this study，We have developed a microporous membrane-based indirect co-culture system forhUCMSCs differentiation，in which epidermal stem cells were seeded on the bottom of microporous membraneand the culture flask of the 6-well dish,hUCMSCs were seeded on the top of microporous membrane．This system allows real-time conditioning of the culture medium with human epidermal cells while still maintaining the complete separation of the two cen types．HUCMSCs in this indirect co-culture system expressed the early markers of epidermal cell lineage,P63，cytokcratin19(CK19)，and β1-integrin．Their morphologies were changed from spindle-like fibroblastic appearances to oblate or irregular shapes under phase contrast microscopy.All these data not only highlight the possibility ofin vitro control of hUCMSCs into epidermal lineage，but also suggest a novel indirect co-culture model for MSCs differentiation．