Therapeutic effect of EGF secreted by human umbilical cord blood-derived mesenchymal stem cells on atopic dermatitis

Human mesenchymal stem cells (MSCs) are emerging as a treatment for atopic dermatitis (AD), which is a common inflammatory skin disorder that affects a large number of people across the world. Treatment of AD using human umbilical cord blood-derived MSCs (hUCB-MSCs) has recently been studied; however, the mechanism underlying the effects of these cells is unclear. This study investigated the effect of epidermal growth factor (EGF) secreted by hUCB-MSCs on AD. hUCB-MSCs secreted a high concentration of EGF compared with other cell types. To elucidate the effect of EGF secreted by hUCB-MSCs, EGF expression was downregulated in hUCB-MSCs using EGF-targeting small interfering RNA, and these cells were co-cultured with keratinocytes, Th2 cells, and mast cells. Depletion of EGF expression disrupted the immunomodulatory effects of hUCB-MSCs on these AD-related inflammatory cells. In a Dermatophagoides farinae-induced AD mouse model, subcutaneous injection of hUCB-MSCs ameliorated gross scoring, histopathologic damage, and mast cell infiltration, and significantly reduced the levels of inflammatory cytokines including interleukin (IL)-4, tumor necrosis factor-α (TNFa), thymus and activation-regulated chemokine (TARC), and IL-22, as well as the serum IgE level. These therapeutic effects were significantly attenuated at all evaluation points in mice injected with EGF-depleted hUCB-MSCs. Taken together, these results suggest that EGF secreted by hUCB-MSCs plays an important role in treatment of AD by regulating the inflammatory response in keratinocytes, Th2 cells, and mast cells.