Serum from patients with asthma potentiates macrophage phagocytosis and human mesenchymal stromal cell therapy in experimental allergic asthma |
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| Affiliation: | 1. Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil;2. National Institute of Science and Technology for Regenerative Medicine, Rio de Janeiro, Brazil;3. Laboratory of Immunological Studies, School of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil;4. Institute of Thoracic Medicine, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil;5. Laboratory of Cellular and Molecular Physiology, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil;6. Biosystems & Integrative Sciences Institute, Faculty of Sciences, University of Lisbon, Lisbon, Portugal;7. Department of Medicine, University of Vermont, College of Medicine, Burlington, Vermont, USA;1. Laboratory of Medical Investigation in Pathogenesis and Directed Therapy in Onco-Immuno-Hematology (LIM-31), Department of Hematology and Cell Therapy, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil;2. Postgraduate program in Medical Science, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil;3. Fundação Pró-Sangue–Hemocentro de Sao Paulo, São Paulo, Brazil;4. Center for Cell-Based Therapy, Regional Blood Center of Ribeirão Preto, Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo, Ribeirão Preto, Brazil;6. Instituto D''Or de Ensino e Pesquisa, São Paulo, Brazil;7. Center for Translational Research in Oncology, Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil;8. Churchill Hospital, Department of Hematology, Churchill Hospital, University of Oxford, Oxford, United Kingdom;1. Medical Sciences Program, University of Brasilia, Brasilia, Distrito Federal, Brazil;2. Program of Evidence for Health Policy and Technologies, Oswaldo Cruz Brasilia Foundation, Brasilia, Distrito Federal, Brazil;4. Interdisciplinary Biosciences Laboratory, Faculty of Medicine, University of Brasília, Brasília, Distrito Federal, Brazil;5. Epidemiology Surveillance, Federal District Health State Department, Brasília, Distrito Federal, Brazil;6. Faculty of Medicine, University of Brasilia, Brasilia, Distrito Federal, Brazil |
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| Abstract: | Background/AimsAlthough several studies have demonstrated that mesenchymal stromal cells (MSCs) exhibit beneficial immunomodulatory properties in preclinical models of allergic asthma, effects on airway remodeling have been controversial. Recent evidence has shown that MSCs modify their in vivo immunomodulatory actions depending on the specific inflammatory environment encountered. Accordingly, we assessed whether the therapeutic properties of human mesenchymal stromal cells (hMSCs) could be potentiated by conditioning these cells with serum (hMSC-serum) obtained from patients with asthma and then transplanted in an experimental model of house dust mite (HDM)-induced allergic asthma.MethodshMSC and hMSC-serum were administered intratracheally 24 h after the final HDM challenge. hMSC viability and inflammatory mediator production, lung mechanics and histology, bronchoalveolar lavage fluid (BALF) cellularity and biomarker levels, mitochondrial structure and function as well as macrophage polarization and phagocytic capacity were assessed.ResultsSerum preconditioning led to: (i) increased hMSC apoptosis and expression of transforming growth factor-β, interleukin (IL)-10, tumor necrosis factor-α–stimulated gene 6 protein and indoleamine 2,3-dioxygenase-1; (ii) fission and reduction of the intrinsic respiratory capacity of mitochondria; and (iii) polarization of macrophages to M2 phenotype, which may be associated with a greater percentage of hMSCs phagocytosed by macrophages. Compared with mice receiving hMSCs, administration of hMSC-serum led to further reduction of collagen fiber content, eotaxin levels, total and differential cellularity and increased IL-10 levels in BALF, improving lung mechanics. hMSC-serum promoted greater M2 macrophage polarization as well as macrophage phagocytosis, mainly of apoptotic hMSCs.ConclusionsSerum from patients with asthma led to a greater percentage of hMSCs phagocytosed by macrophages and triggered immunomodulatory responses, resulting in further reductions in both inflammation and remodeling compared with non-preconditioned hMSCs. |
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