Therapeutic effects of extracellular vesicles derived from mesenchymal stem cells primed with disease-conditioned-immune cells in systemic lupus erythematosus.
Eun Wha Choi, Il Seob Shin, I-Rang Lim, Jihye Lee, Bongkum Choi, Sungjoo Kim
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Abstract
Background: Systemic lupus erythematosus (SLE) is an incurable chronic autoimmune disease of unknown etiology. Therefore, the development of new treatments is urgently needed. This study aimed to investigate the therapeutic effects of extracellular vesicles (EV) derived from immortalized mesenchymal stem cells (iMSCs) primed with conditioned media obtained from disease-conditioned immune cells (CM-EV) and iMSC-derived EV (ASC-EV) in a murine model of SLE.
Methods: Female NZB/W F1 mice were divided into the control (C, n = 15), ASC-EV (E, n = 15), and CM-EV (CM, n = 15) groups. Mice in the C, E, and CM groups were intravenously administered saline, ASC-EV, and CM-EV, respectively, once weekly from 6 to 42 weeks of age.
Results: Compared to the ASC-EV, the CM-EV showed a significant increase in TGF-β1 production and miR-155-5p and miR-142-3p expression. CM-EV treatment increased survival, decreased anti-dsDNA antibody levels, and ameliorated renal histopathology. Although ASC-EV treatment significantly reduced the incidence of severe proteinuria and improved renal histopathology, it did not significantly improve survival rate. ASC-EV or CM-EV treatment significantly decreased the proportion of pro-inflammatory macrophages (CD11c + CD206-; M1) and M1:M2 ratio. Additionally, CM-EV treatment significantly increased the expression of anti-inflammatory macrophages (CD11c-CD206 + ; M2). Moreover, CM-EV treatment significantly decreased the expression of lupus-specific miRNAs (miR-182-5p and miR-183-5p) in the spleen.
Conclusions: EV derived from iMSCs primed with conditioned media obtained from disease-conditioned immune cells exert immunomodulatory effects and ameliorate SLE in a murine model.
期刊介绍：
Established in 1999, Arthritis Research and Therapy is an international, open access, peer-reviewed journal, publishing original articles in the area of musculoskeletal research and therapy as well as, reviews, commentaries and reports. A major focus of the journal is on the immunologic processes leading to inflammation, damage and repair as they relate to autoimmune rheumatic and musculoskeletal conditions, and which inform the translation of this knowledge into advances in clinical care. Original basic, translational and clinical research is considered for publication along with results of early and late phase therapeutic trials, especially as they pertain to the underpinning science that informs clinical observations in interventional studies.
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