Serum from Asthmatic Mice Potentiates the Therapeutic Effects of Mesenchymal Stromal Cells in Experimental Allergic Asthma. (13th November 2018)

• Record Type: Journal Article
• Authors: Abreu, Soraia C.; Xisto, Debora G.; Oliveira, Tainá B.; Blanco, Natalia G.; Castro, Lígia Lins; Kitoko, Jamil Zola; Olsen, Priscilla C.; Lopes-Pacheco, Miquéias; Morales, Marcelo M.; Weiss, Daniel J.; Rocco, Patricia R.M.
• Is Part Of: Stem cells translational medicine. Volume 8:Number 3(2019)
• Page Start: 301
• Page End: 312
• Publication Date: 2018-11-13
• Subjects: Bone marrow stromal cells -- Cell therapy -- Lung -- Animal models -- Eosinophils -- Macrophages; Stem cells -- Periodicals; Regenerative medicine -- Periodicals; Periodicals; 616.0277405
• DOI: 10.1002/sctm.18-0056
• Languages: English
• ISSNs: 2157-6564

Abstract

Abstract: 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 : Abstract : Compared to unstimulated or bronchoalveolar lavage fluid (BALF)-stimulated MSCs, serum-stimulated MSCs reduced levels of interleukin (IL)-4, IL-13, and eotaxin, and collagen fiber content, while increasing IL-10. Serum stimulation yielded higher MSC apoptosis, expressions of: transforming growth factor (TGF)-β, IFN (interferon)-γ, IL-10, TSG6 (tumor necrosis factor-α-stimulated gene 6), IDO (indoleamine 2, 3-dioxygenase)-1, and IL-1RN, and polarization of macrophages to the M2 phenotype.