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

Author:

Abreu Soraia C.1,Xisto Debora G.1,Oliveira Tainá B.1,Blanco Natalia G.1,Castro Lígia Lins1,Kitoko Jamil Zola12,Olsen Priscilla C.2,Lopes-Pacheco Miquéias134,Morales Marcelo M.24,Weiss Daniel J.5,Rocco Patricia R.M.14

Affiliation:

1. Laboratory of Pulmonary Investigation Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil

2. Laboratory of Clinical Bacteriology and Immunology School of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil

3. 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

4. National Institute of Science and Technology for Regenerative Medicine, Rio de Janeiro, Brazil

5. Department of Medicine University of Vermont, College of Medicine, Burlington, Vermont, USA

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

Funder

National Institute of Science and Technology for Regenerative Medicine

Coordination for the Improvement of Higher Education Personnel

Brazilian Ministry of Health

Department of Science and Technology

Rio de Janeiro State Research Foundation

Brazilian Council for Scientific and Technological Development

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Developmental Biology,General Medicine

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