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A7195 - Eicosapentaenoic Acid Potentiates the Effects of Bone Marrow-Derived Mesenchymal Stromal Cell Therapy in Experimental Allergic Asthma
Author Block: S. Abreu1, M. Pacheco1, D. Xisto1, A. L. Silva1, J. Z. Kitoko1, T. B. de Oliveira1, N. Amorim2, V. Martins3, C. Gonçalves-de-Albuquerque4, H. C. Faria-Neto4, P. C. Olsen5, M. Morales6, D. J. Weiss7, B. L. Diaz2, P. R. Rocco1; 1Carlos Chagas Filho Institute of Biophysics, Laboratory of Pulmonary Investigation, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil, 2Carlos Chagas Filho Institute of Biophysics, Laboratory of Inflammation, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil, 3Department of Pathology, University of Sao Paulo, Sao Paulo, Brazil, 4Laboratory of Immunopharmacology, FIOCRUZ, Rio de Janeiro, Brazil, 5Laboratory of Clinical Bacteriology and Immunology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil, 6Carlos Chagas Filho Institute of Biophysics, Laboratory of Cellular and Molecular Physiology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil, 7Department of Medicine, University of Vermont, Burlington, VT, United States.
RATIONALE: Asthma is an emerging global health issue. Although symptoms can be controlled, there are no effective therapeutic interventions to repair the chronic airway remodeling that occurs. Systemic administration of mesenchymal stromal cells (MSCs) mitigates lung inflammation in experimental allergic asthma; however, effects on the airway remodeling process are limited. Metabolites derived from eicosapentaenoic acid (EPA) supplementation may stimulate MSCs and potentiate their anti-inflammatory and antifibrogenic properties. The aim of this study was to investigate whether pretreatment with EPA potentiates the therapeutic properties of MSCs in experimental allergic asthma. METHODS: Allergic asthma was induced in 32 C57BL/6 mice by intranasal challenges with house dust mite (HDM) extract, 25 µg in 25 µL saline, three times weekly for three weeks. Control animals received only saline (25 µL, n=8) using the same protocol. Twenty-four hours after the last challenge, HDM animals were further randomized to receive saline (50 μL, SAL, n=8/each), bone marrow-derived MSCs (105, MSCs, n=6/each), or bone marrow-derived MSCs stimulated with PUFA (105, MSC-EPA, n=6/each), for 6h, intratracheally. Three days after cellular therapy, lung mechanics and histology and cells, protein, and inflammatory markers in bronchoalveolar lavage fluid (BALF), thymus, lymph nodes, and bone marrow were analyzed. RESULTS: Nonstimulated and EPA-stimulated MSCs similarly reduced eosinophil and macrophage counts in bone marrow, thymus cellularity, and elastic fiber content in lungs. Nonstimulated MSCs improved lung mechanics and reduced BALF interleukin (IL)-13 and vascular endothelial growth factor (VEGF) levels, as well as total and differential cell counts. EPA-stimulated MSCs further ameliorated those parameters and reduced bronchoconstriction, alveolar collapse, BALF IL-4 levels, bone marrow neutrophil and total cell counts, lymph node cellularity, collagen fiber content, mucus-filled cells, and M1 macrophage count in lungs, while increasing BALF IL-10 and M2 macrophages, compared to nonstimulated MSCs. EPA-stimulated MSCs may lead to these beneficial effects by increasing resolvin, prostaglandin E2, IL-10, and transforming growth factor-β secretion. CONCLUSION: EPA supplementation may be a novel strategy to potentiate MSC effects in experimental allergic asthma, yielding superior reductions in both inflammation and remodeling.