Effects of Human Mesenchymal Stem Cells Transduced with Superoxide Dismutase on Imiquimod-Induced Psoriasis-Like Skin Inflammation in Mice

Abstract

Aims: The immunomodulatory and anti-inflammatory properties of mesenchymal stem cells (MSCs) have been proposed in several autoimmune diseases and successfully tested in animal models, but their contribution to psoriasis and underlying pathways remains elusive. Likewise, an increased or prolonged presence of reactive oxygen species and aberrant antioxidant systems in skin are known to contribute to the development of psoriasis and therefore effective antioxidant therapy is highly required. We explored the feasibility of using extracellular superoxide dismutase (SOD3)-transduced allogeneic MSCs as a novel therapeutic approach in a mouse model of imiquimod (IMQ)-induced psoriasis-like inflammation and investigated the poorly understood underlying mechanism. In addition, the chronicity and late-phase response of inflammation were evaluated during continued activation of antigen receptors by applying a booster dose of IMQ. Results: Subcutaneous injection of allogeneic SOD3-transduced MSCs significantly prevented psoriasis development in our IMQ-induced mouse model, likely through a suppression of proliferation and infiltration of various effector cells into skin with a concomitant modulated cytokine and chemokine expression and inhibition of signaling pathways such as tolllike receptor-7, nuclear factor-kappa B, p38 mitogen-activated kinase, and Janus kinase-signal transducer and activator of transcription, as well as adenosine receptor activation. Innovation and Conclusion: Our data offer a novel therapeutic approach to chronic inflammatory skin diseases such as psoriasis by leveraging immunomodulatory effects of MSCs as well as SOD3 expression.This research was supported by the Bio and Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science, ICT and Future Planning, Republic of Korea (Grant No. NRF-2013M3A9A9050567), and the Korea Health Technology R&D project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (Grant No. HI12C17990100)