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Mesenchymal stem/stromal cell-based therapy fails to provide clinical benefit in K/BxN serum transfer-induced arthritis

M Lopez-Santalla(1,2) C Conde(3) A Rodriguez-Trillo(3) J A Bueren(1,2) M I Garin(1,2)

1:Division of Hematopoietic Innovative Therapies, Biomedical Innovation Unit, Centro de Investigaciones Energéticas Medioambientales y Tecnológicas (CIEMAT) and Centre for Biomedical Network Research on Rare Diseases (CIBER-ER); 2:Advanced Therapy Unit, Health Research Institute-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain.; 3:Laboratorio de Reumatología. Experimental y Observacional, Instituto de Investigación Sanitaria de Santiago (IDIS), Hospital Clínico Universitario de Santiago de Compostela (CHUS), SERGAS, Santiago de Compostela, Spain

Rheumatoid arthritis (RA) is an immune-mediated disorder caused by loss of immunological self-tolerance that generates systemic and chronic inflammation in synovial tissues that finally leads to cartilage and bone destruction. Despite advances in understanding the aetiology of RA and novel biologic drugs, a substantial number of individuals with RA remains intolerant or resistant to these therapies. Hence, development of new therapeutic approaches are highly needed and, in this sense, mesenchymal stem/stromal cells (MSCs)-based therapy has emerged as a new alternative treatment for RA patients thanks to their well described immunomodulatory properties. The majority of preclinical studies in MSC-based therapy have been conducted using the well-known collagen-induced arthritis (CIA) mouse model. However, the low incidence of the disease in commonly used mouse strains in immunological studies, the prolonged induction phase, together with the restriction of mouse strains that are susceptible to developing arthritis have led to the development of alternative experimental models of RA. In this sense, the K/BxN serum transfer-induced arthritis (STIA) model has been developed as a very useful in vivo model that mimics many human RA disease characteristics. In this study, we aimed to evaluate the immunomodulatory potential of allogeneic adipose-derived MSC-based therapy in the K/BxN STIA model. Unexpectedly, our data suggest that allogeneic adipose-derived MSC therapy was unable of modulating the progression of the disease despite various experimental parameters tested.

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