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Therapeutic administration of bone marrow‐derived mesenchymal stromal cells reduces airway inflammation without up‐regulating Tregs in experimental asthma
Author(s) -
Kitoko J. Z.,
de Castro L. L.,
Nascimento A. P.,
Abreu S. C.,
Cruz F. F.,
Arantes A. C.,
Xisto D. G.,
Martins M. A.,
Morales M. M.,
Rocco P. R. M.,
Olsen P. C.
Publication year - 2018
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.13048
Subject(s) - mesenchymal stem cell , medicine , immunology , inflammation , bone marrow , bronchoalveolar lavage , ovalbumin , stromal cell , lung , pathology , immune system
Summary Background Prophylactic administration of mesenchymal stromal cells ( MSC s) derived from adipose ( AD ‐ MSC ) and bone marrow tissue ( BM ‐ MSC ) in ovalbumin‐induced asthma hinders inflammation in a Treg‐dependent manner. It is uncertain whether MSC s act through Tregs when inflammation is already established in asthma induced by a clinically relevant allergen. Objective Evaluate the effect of therapeutic administration of MSC s on inflammation and Treg cells in house dust mite ( HDM )‐induced asthma. Methods BM ‐ MSC s and AD ‐ MSC s were administered intratracheally to C57 BL /6 mice 1 day after the last HDM challenge. Lung function, remodelling and parenchymal inflammation were assayed 3 or 7 days after MSC s treatment, through invasive plethysmography and histology, respectively. Bronchoalveolar lavage fluid ( BALF ) and mediastinal lymph nodes ( mLN s) were assessed regarding the inflammatory profile by flow cytometry, ELISA and qRT‐PCR. MSC s were studied regarding their potential to induce Treg cells from primed and unprimed lymphocytes in vitro. Results BM ‐ MSC s, but not AD ‐ MSC s, reduced lung influx of eosinophils and B cells and increased IL ‐10 levels in HDM ‐challenged mice. Neither BM ‐ MSC s nor AD ‐ MSC s reduced lung parenchymal inflammation, airway hyperresponsiveness or mucus hypersecretion. BM ‐ MSC s and AD ‐ MSC s did not up‐regulate Treg cell counts within the airways and mLN s, but BM ‐ MSC s decreased the pro‐inflammatory profile of alveolar macrophages. Co‐culture of BM ‐ MSC s and AD ‐ MSC s with allergen‐stimulated lymphocytes reduced Treg cell counts in a cell‐to‐cell contact‐independent manner, although co‐culture of both MSC s with unprimed lymphocytes up‐regulated Treg cell counts. Conclusions MSC s therapeutically administered exert anti‐inflammatory effects in the airway of HDM ‐challenged mice, but do not ameliorate lung function or remodelling. Although MSC pre‐treatment can increase Treg cell numbers, it is highly unlikely that the MSC s will induce Treg cell expansion when lymphocytes are allergenically primed in an established lung inflammation.