Mesenchymal stromal 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. Through 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 (MSC_hCCR7 or MSC_hCCR4) that increased the migration capacity into the secondary lymphoid organ or skin, respectively. And we investigated the effect of MSC_hCCR7 or MSC_hCCR4 on the therapeutic efficacy in AD mice model.
We obtained first MSC_hCCR7 and MSC_hCCR4 have maintained stem cell characteristics and immunoregulatory activities in vitro. Second, the homing ability of MSC_hCCR7 to skin lesions and DLNs was increased significantly compared to those of control MSC in AD mice model. Third, MSC_hCCR7 and MSC_hCCR4 reduced epidermal thickness and significantly decreased serum levels of IgE in AD mice model. In addition, IL-4 expression was also significantly suppressed by MSC_hCCR7 and MSC_hCCR4 in both the lymph node and skin.
These results suggest that MSC_hCCR7 and MSC_hCCR4 could cure AD fundamentally by blocking the Th2 effector cells in either LN or skin tissues. In conclusion, MSC_hCCR7 and MSC_hCCR4 may show better therapeutic effects compared to the control MSC. Therefore, increasing migration capacity into the secondary lymphoid organ or skin lesion might be used as a novel stem cell therapeutic strategy to target AD.