Open AccessBone Marrow, Adipose, and Lung Tissue‐Derived Murine Mesenchymal Stromal Cells Release Different Mediators and Differentially Affect Airway and Lung Parenchyma in Experimental Asthma
Author(s) -
Abreu Soraia C.,
Antunes Mariana A.,
Xisto Debora G.,
Cruz Fernanda F.,
Branco Vivian C.,
Bandeira Elga,
Zola Kitoko Jamil,
de Araújo Almair F.,
DellatorreTexeira Ludmilla,
Olsen Priscilla C.,
Weiss Daniel J.,
Diaz Bruno L.,
Morales Marcelo M.,
Rocco Patricia R. M.
Publication year - 2017
Publication title -
stem cells translational medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.781
H-Index - 71
eISSN - 2157-6580
pISSN - 2157-6564
DOI - 10.1002/sctm.16-0398
Subject(s) - mesenchymal stem cell , medicine , lung , bone marrow , vascular endothelial growth factor , adipose tissue , pathology , immunology , cancer research , vegf receptors
Mesenchymal stromal cells (MSCs) from different sources have differential effects on lung injury. To compare the effects of murine MSCs from bone marrow (BM), adipose tissue (AD), and lung tissue (LUNG) on inflammatory and remodeling processes in experimental allergic asthma, female C57BL/6 mice were sensitized and challenged with ovalbumin (OVA) or saline (C). Twenty‐four hours after the last challenge, mice received either saline (50 µl, SAL), BM‐MSCs, AD‐MSCs, or LUNG‐MSCs (10 5 cells per mouse in 50 µl total volume) intratracheally. At 1 week, BM‐MSCs produced significantly greater reductions in resistive and viscoelastic pressures, bronchoconstriction index, collagen fiber content in lung parenchyma (but not airways), eosinophil infiltration, and levels of interleukin (IL)‐4, IL‐13, transforming growth factor (TGF)‐β, and vascular endothelial growth factor (VEGF) in lung homogenates compared to AD‐MSCs and LUNG‐MSCs. Only BM‐MSCs increased IL‐10 and interferon (IFN)‐γ in lung tissue. In parallel in vitro experiments, BM‐MSCs increased M2 macrophage polarization, whereas AD‐MSCs and LUNG‐MSCs had higher baseline levels of IL‐4, insulin‐like growth factor (IGF), and VEGF secretion. Exposure of MSCs to serum specimens obtained from asthmatic mice promoted reductions in secretion of these mediators, particularly in BM‐MSCs. Intratracheally administered BM‐MSCs, AD‐MSCs, and LUNG‐MSCs were differentially effective at reducing airway inflammation and remodeling and improving lung function in the current model of allergic asthma. In conclusion, intratracheal administration of MSCs from BM, AD, and LUNG were differentially effective at reducing airway inflammation and remodeling and improving lung function comparably reduced inflammation and fibrogenesis in this asthma model. However, altered lung mechanics and lung remodeling responded better to BM‐MSCs than to AD‐MSCs or LUNG‐MSCs. Moreover, each type of MSC was differentially affected in a surrogate in vitro model of the in vivo lung environment. S tem C ells T ranslational M edicine 2017;6:1557–1567