Serum from Asthmatic Mice Potentiates the Therapeutic Effects of Mesenchymal Stromal Cells in Experimental Allergic Asthma.

Autor: Abreu SC; Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil., Xisto DG; Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil., de Oliveira TB; Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil., Blanco NG; Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil., de Castro LL; Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil., Kitoko JZ; Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.; Laboratory of Clinical Bacteriology and Immunology, School of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil., Olsen PC; Laboratory of Clinical Bacteriology and Immunology, School of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil., Lopes-Pacheco M; Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.; Laboratory of Cellular and Molecular Physiology, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.; National Institute of Science and Technology for Regenerative Medicine, Rio de Janeiro, Brazil., Morales MM; Laboratory of Clinical Bacteriology and Immunology, School of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.; National Institute of Science and Technology for Regenerative Medicine, Rio de Janeiro, Brazil., Weiss DJ; Department of Medicine, University of Vermont, College of Medicine, Burlington, Vermont, USA., Rocco PRM; Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.; National Institute of Science and Technology for Regenerative Medicine, Rio de Janeiro, Brazil.
Jazyk: angličtina
Zdroj: Stem cells translational medicine [Stem Cells Transl Med] 2019 Mar; Vol. 8 (3), pp. 301-312. Date of Electronic Publication: 2018 Nov 13.
DOI: 10.1002/sctm.18-0056
Abstrakt: Asthma is a chronic inflammatory disease characterized by airway inflammation and remodeling, which can lead to progressive decline of lung function. Although mesenchymal stromal cells (MSCs) have shown beneficial immunomodulatory properties in preclinical models of allergic asthma, effects on airway remodeling have been limited. Mounting evidence suggests that prior exposure of MSCs to specific inflammatory stimuli or environments can enhance their immunomodulatory properties. Therefore, we investigated whether stimulating MSCs with bronchoalveolar lavage fluid (BALF) or serum from asthmatic mice could potentiate their therapeutic properties in experimental asthma. In a house dust mite (HDM) extract asthma model in mice, unstimulated, asthmatic BALF-stimulated, or asthmatic serum-stimulated MSCs were administered intratracheally 24 hours after the final HDM challenge. Lung mechanics and histology; BALF protein, cellularity, and biomarker levels; and lymph-node and bone marrow cellularity were assessed. Compared with unstimulated or BALF-stimulated MSCs, serum-stimulated MSCs further reduced BALF levels of interleukin (IL)-4, IL-13, and eotaxin, total and differential cellularity in BALF, bone marrow and lymph nodes, and collagen fiber content, while increasing BALF IL-10 levels and improving lung function. Serum stimulation led to higher MSC apoptosis, expression of various mediators (transforming growth factor-β, interferon-γ, IL-10, tumor necrosis factor-α-stimulated gene 6 protein, indoleamine 2,3-dioxygenase-1, and IL-1 receptor antagonist), and polarization of macrophages to M2 phenotype. In conclusion, asthmatic serum may be a novel strategy to potentiate therapeutic effects of MSCs in experimental asthma, leading to further reductions in both inflammation and remodeling than can be achieved with unstimulated MSCs. Stem Cells Translational Medicine 2019;8:301&312.
(© 2018 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)
Databáze: MEDLINE
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