A novel Therapeutic Strategy of Mesenchymal Stem Cells to Target Atopic Dermatitis

초록

Mesenchymal steml cells (MSCs) are known to suppress immune cells activation and proliferation. Due to their role of immune cell suppression, MSCs have been suggested as a novel medical therapeutics to prevent autoimmune diseases. Previous study, we demonstrated that MSC has therapeutic efficacy in ovalbumin-induced atopic dermatitis (AD) mice models and this therapeutic efficacy was related to the homing of systemically infused MSC to skin lesions and draining lymph nodes (DLNs). Thus, we hypothesized that the use of MSC enhanced the homing ability to skin lesions and DLN may improve their therapeutic efficacy in AD. Using lentiviral system, we engineered human-chemokine receptor 7 (hCCR7) and human-chemokine receptor 4 (hCCR4) genes into murine MSCs that increased the migration capacity into the secondary lymphoid organ or skin, respectively. And we investigated the effect of hCCR7 or hCCR4MSCs on the therapeutic efficacy in AD mice model. We obtained first hCCR7 and hCCR4MSC have maintained immunoregulatory activities in vitro. Second, the homing ability of hCCR7MSC to DLNs and hCCR4MSC to skin lesions was increased significantly compared to those of control MSC in AD mice model. Third, hCCR4MSC reduced epidermal thickness and significantly decreased the serum levels of IgE in AD mice model. In addition, IL-4 expression was also significantly suppressed in LNs by hCCR7MSC and in skin by hCCR4MSC. These results suggest that hCCR4MSC which migrate into the skin lesion might be better for the treatment of AD compared to the hCCR7MSC and the control MSC. In conclusion, increasing migration capacity into the skin lesion might be used as a novel stem cell therapeutic strategy to target AD.