O021 Mesenchymal stem cell-derived extracellular vesicles: a novel therapeutic option in systemic sclerosis

Introduction Systemic sclerosis (SSc) is a rare intractable autoimmune disease, with unmet medical need. Cell therapy using mesenchymal stem cells (MSC) is a promising approach, and we recently reported its efficacy in a murine model of SSc induced by hypochlorite (HOCl). Since MSC act primarily through the secretion of soluble factors released within extracellular vesicles (EV), the use of EV instead of cells seems an attractive alternative. Herein, we compared the effects of two types of EV, exosomes and microparticles, in HOCl-induced SSc. Objectives Herein, we compared the effects of two types of EV, exosomes and microparticles, in HOCl-induced SSc. Methods BALB/c mice were challenged with daily intradermal HOCl injections during 6 weeks to induce SSc. Each group was treated at mid-experiment with infusions of 2.5×105 murine MSC, 250 ng of exosomes or microparticles isolated from IFNγ-activated or non-activated (NA) MSC. We measured skin thickness every week. At euthanasia (d42), we analysed the expression of fibrotic and inflammatory markers (collagens 1 and 3, αSma, TGFβ, MMP 1 and 9, TIMP1, IL1β, IL6, TNFα) in lungs and skin samples using RT-qPCR. Results Mice treated with each subtype of EV displayed lower clinical scores, less histological lesions, lower expression of fibrotic and inflammatory markers, with enhanced expression of remodelling parameters in skin and lung tissues. The observed effects were similar to those obtained with MSC. No difference was noted between NA and IFNγ-activated EV. Conclusions MSC-derived EV display potent antifibrotic properties in murine SSc. This new acellular therapy represents a promising approach in this disease. Disclosure of interest None declared