FRI0510 THE EFFECT AND MECHANISM OF HUMAN UMBILICAL CORD MESENCHYMAL STEM CELLS-DERIVED EXOSOMES ON BONE DESTRUCTION OF COLLAGEN INDUCED ARTHRITIS RATS

Background Rheumatoid arthritis (RA) is a highly disabling autoimmune disease, characterized by destruction of the cartilage and bone, which is difficult to reverse. mesenchymal stem cells-derived exosomes (Mesenchymal stem cells-derived Exos) is a kind of extracellular vesicle, produced by MSCs in resting or stress state, which can simulate the tissue repair effect of its maternal cells and may be a new breakthrough point in the treatment of RA bone destruction. Objectives Study the effect of human umbilical cord mesenchymal stem cells derived exosomes(hUCMSC-exos) on bone destruction in Collagen induced arthritis (CIA) rats. Methods 1. After isolated by differential centrifugation, hUCMSCs was cultured in vitro, which was identified by morphology and surface markers.2. Grouping: The CIA rats were randomly divided into CIA group, MTX group, hUCMSCs group, hUCMSC-exos low concentration group, hUCMSC-exos medium concentration group, hUCMSC-exos high concentration group, and a healthy control group.3. Efficacy evaluation: the efficacy of hUCMSC-exos on CIA rats was evaluated by measuring joint swelling, arthritis index, micro-ct scanning and pathological score. The expression levels of RANKL and OPG in the serum of rats in each group were detected by high-throughput flow,multi-factor detection technique or ELISA method, and the levels of the above factors in the synovial tissue of the ankle were detected by immunohistochemical detection technique, and the mRNA levels were detected by RT-PCR. Results 1. Effect evaluation: hUCMSC-exos can improve the arthritis index (AI) of CIA rats, and no definite side effect been find. In addition to hUCMSC-exos low concentration group, the joint synovial hyperplasia and inflammatory cell infiltration degree of each treatment group were significantly improved, comparing with that of CIA group. The Results of Micro-ct scanning suggested that the degree of osteoporosis in each intervention group was significantly improved comparing with that in the CIA group, and the improvement degree of hUCMSCs groups,MTX groups and hUCMSC-exos high concentration group was similar.2.The detection of bone metabolism factor in Serum and synovial tissue: medium and high concentrations of hUCMSC-exos, hUCMSCs group and MTX group could down-regulate the level of RANKL in serum and synovial tissues of CIA rats, and raise the level of OPG, and the effect of hUCMSC-exos in high concentration group was slightly obvious. Conclusion: hUCMSC-exos can improve bone destruction in CIA rats, and it is safe. hUCMSC-exos can mimic its mother cells and exert an inhibitory effect on bone destruction by regulating the imbalance of RANKL/OPG, and the effect is equal or better than its mother cells, and the high concentration group is superior to the low concentration group. References [1] Aghajani NA, Lerman LO, Eirin A. Mesenchymal stem cell-derived extracellular vesicles for kidney repair: current status and looming challenges. STEM CELL RES THER2017;8(1):273. [2] Calabresi E, Petrelli F, Bonifacio AF, Puxeddu I, Alunno A. One year in review 2018: pathogenesis of rheumatoid arthritis. CLIN EXP RHEUMATOL2018;36(2):175-84. [3] Emori T, Hirose J, Ise K, Yomoda JI, Kasahara M, Shinkuma T, Yoshitomi H, Ito H, Hashimoto M, Sugahara S, Fujita H, Yamamoto N, Morita Y, Narumiya S, Aramori I. Constitutive Activation of Integrin alpha9 Augments Self-Directed Hyperplastic and Proinflammatory Properties of Fibroblast-like Synoviocytes of Rheumatoid Arthritis. J IMMUNOL2017;199(10):3427-36. [4] Potter DR, Miyazawa BY, Gibb SL, Deng X, Togaratti PP, Croze RH, Srivastava AK, Trivedi A, Matthay M, Holcomb JB, Schreiber MA, Pati S. Mesenchymal stem cell-derived extracellular vesicles attenuate pulmonary vascular permeability and lung injury induced by hemorrhagic shock and trauma. J Trauma Acute Care Surg2018;84(2):245-56. Disclosure of Interests None declared