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Enhanced therapeutic effect of mesenchymal stem/stromal cells overexpressing CXCR4 and IL10 in experimental colitis

M Lopez-Santalla(1) R M Yañez(1) R Hervas-Salcedo(1) M Fernandez-Garcia(1) J A Bueren(1) M I Garin(1)

1:Division of Hematopoietic Innovative Therapies, Biomedical Innovation Unit, Centro de Investigaciones Energéticas Medioambientales y Tecnológicas (CIEMAT), Centre for Biomedical Network Research on Rare Diseases (CIBER-ER) and Advanced Therapy Unit, Health Research Institute-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain.

Inflammatory bowel diseases (IBD) consist on chronic inflammation of intestinal mucosa frequently associated to a significant increase in the risk of colitis-associated colon cancer. Multiple factors including environmental, genetic background and microbiota are related to its origin and aggravation. Current available treatments aim at reducing inflammation to avoid disease recurrence or to prolong clinical remission periods. Despite recent advances, no treatment is fully effective for many refractory patients, so that surgery remains as the only alternative. New therapeutic approaches are highly needed and, in this sense, mesenchymal stem/stromal cell (MSCs)-based therapy represents a promising option for unmet medical needs due to their immunomodulatory and regenerative properties. Preclinical and clinical data from animal models and clinical trials have demonstrated that MSC therapy is safe, although a significant heterogeneity exists in terms of therapeutic efficacy in the clinic. To enhance the therapeutic potential of MSC-based therapy, we have genetically modified adipose-derived MSCs with a lentiviral vector carrying the CXCR4 and interleukin 10 genes aiming to enhance their migration to inflamed tissues together with the improved anti-inflammatory potential. The therapeutic efficacy of CXCR4/IL10-expressing MSCs was tested using the dextran suphate sodium (DSS)-induced colitis model. A single dose of CXCR4/IL10-MSCs showed significant reduction in the disease activity index and incidence of colitis when compared with non-genetically modified MSCs suggesting that CXCR4/IL10-expressing MSCs may represent a more potent MSC-based cell therapy product for treatment inflammatory bowel diseases.

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