Inflammation-Targeting Mesenchymal Stem Cells Combined with Photothermal Treatment Attenuate Severe Joint Inflammation.

Current clinical therapeutic efficacy for the treatment of osteo- and rheumatoid-arthritis is obviously limited. Although mesenchymal stem cells (MSCs) are considered as a source of promising regenerative therapy, un-modified MSCs or genetically engineered MSCs injected in vivo restrict their clinical utility because of the low drug efficacy and unpredicted side effect, respectively. Herein, a strategy to enhance the migration efficacy of MSCs to inflamed joints via an inflammation-mediated education process was demonstrated. To reinforce the limited anti-inflammatory activity of MSCs, gold nano-star loaded with triamcinolone are conjugated to MSC. Furthermore, near-infrared laser-assisted photothermal therapy (PTT) induced by gold nano-star significantly elevate the anti-inflammatory efficacy of the developed drugs, even in advanced stage arthritis model. An immunological regulation mechanism study of PTT is first suggested in this study; the expression of the interleukin 22 receptor, implicated in the pathogenesis of arthritis, was downregulated in T lymphocytes by PTT, and Th17 differentiation from naïve CD4 T cell was inhibited. Collectively, inflammation-targeting MSCs conjugated with triamcinolone-loaded gold nano-star promote the repolarization of macrophages and decrease neutrophil recruitment in joints. In addition, Edu-MSCs-AuS-TA significantly alleviate arthritis-associated pain and improve general locomotor activity, and more importantly, induced cartilage regeneration even for severe stages of arthritis model. This article is protected by copyright. All rights reserved.