J Z Kitoko1,2,3, L L de Castro2,3, A P Nascimento1, S C Abreu2, F F Cruz2, A C Arantes4, D G Xisto2,3, M A Martins4, M M Morales3, P R M Rocco2, P C Olsen1. 1. Laboratory of Clinical Bacteriology and Immunology, Faculty of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. 2. Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. 3. Laboratory of Cellular and Molecular Physiology, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. 4. Laboratory of Inflammation, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
Abstract
BACKGROUND: Prophylactic administration of mesenchymal stromal cells (MSCs) 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 MSCs act through Tregs when inflammation is already established in asthma induced by a clinically relevant allergen. OBJECTIVE: Evaluate the effect of therapeutic administration of MSCs on inflammation and Treg cells in house dust mite (HDM)-induced asthma. METHODS: BM-MSCs and AD-MSCs were administered intratracheally to C57BL/6 mice 1 day after the last HDM challenge. Lung function, remodelling and parenchymal inflammation were assayed 3 or 7 days after MSCs treatment, through invasive plethysmography and histology, respectively. Bronchoalveolar lavage fluid (BALF) and mediastinal lymph nodes (mLNs) were assessed regarding the inflammatory profile by flow cytometry, ELISA and qRT-PCR. MSCs were studied regarding their potential to induce Treg cells from primed and unprimed lymphocytes in vitro. RESULTS: BM-MSCs, but not AD-MSCs, reduced lung influx of eosinophils and B cells and increased IL-10 levels in HDM-challenged mice. Neither BM-MSCs nor AD-MSCs reduced lung parenchymal inflammation, airway hyperresponsiveness or mucus hypersecretion. BM-MSCs and AD-MSCs did not up-regulate Treg cell counts within the airways and mLNs, but BM-MSCs decreased the pro-inflammatory profile of alveolar macrophages. Co-culture of BM-MSCs and AD-MSCs with allergen-stimulated lymphocytes reduced Treg cell counts in a cell-to-cell contact-independent manner, although co-culture of both MSCs with unprimed lymphocytes up-regulated Treg cell counts. CONCLUSIONS: MSCs 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 MSCs will induce Treg cell expansion when lymphocytes are allergenically primed in an established lung inflammation.
BACKGROUND: Prophylactic administration of mesenchymal stromal cells (MSCs) 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 MSCs act through Tregs when inflammation is already established in asthma induced by a clinically relevant allergen. OBJECTIVE: Evaluate the effect of therapeutic administration of MSCs on inflammation and Treg cells in house dust mite (HDM)-induced asthma. METHODS: BM-MSCs and AD-MSCs were administered intratracheally to C57BL/6 mice 1 day after the last HDM challenge. Lung function, remodelling and parenchymal inflammation were assayed 3 or 7 days after MSCs treatment, through invasive plethysmography and histology, respectively. Bronchoalveolar lavage fluid (BALF) and mediastinal lymph nodes (mLNs) were assessed regarding the inflammatory profile by flow cytometry, ELISA and qRT-PCR. MSCs were studied regarding their potential to induce Treg cells from primed and unprimed lymphocytes in vitro. RESULTS: BM-MSCs, but not AD-MSCs, reduced lung influx of eosinophils and B cells and increased IL-10 levels in HDM-challenged mice. Neither BM-MSCs nor AD-MSCs reduced lung parenchymal inflammation, airway hyperresponsiveness or mucus hypersecretion. BM-MSCs and AD-MSCs did not up-regulate Treg cell counts within the airways and mLNs, but BM-MSCs decreased the pro-inflammatory profile of alveolar macrophages. Co-culture of BM-MSCs and AD-MSCs with allergen-stimulated lymphocytes reduced Treg cell counts in a cell-to-cell contact-independent manner, although co-culture of both MSCs with unprimed lymphocytes up-regulated Treg cell counts. CONCLUSIONS: MSCs 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 MSCs will induce Treg cell expansion when lymphocytes are allergenically primed in an established lung inflammation.
Authors: Hananda A Poggio; Mariana A Antunes; Nazareth N Rocha; Jamil Z Kitoko; Marcelo M Morales; Priscilla C Olsen; Miquéias Lopes-Pacheco; Fernanda F Cruz; Patricia R M Rocco Journal: Stem Cell Res Ther Date: 2018-11-08 Impact factor: 6.832
Authors: Soraia C Abreu; Debora G Xisto; Tainá B de Oliveira; Natalia G Blanco; Lígia Lins de Castro; Jamil Zola Kitoko; Priscilla C Olsen; Miquéias Lopes-Pacheco; Marcelo M Morales; Daniel J Weiss; Patricia R M Rocco Journal: Stem Cells Transl Med Date: 2018-11-13 Impact factor: 6.940
Authors: Adriana L da Silva; Gisele P de Oliveira; Namho Kim; Fernanda F Cruz; Jamil Z Kitoko; Natalia G Blanco; Sabrina V Martini; Justin Hanes; Patricia R M Rocco; Jung Soo Suk; Marcelo M Morales Journal: Sci Adv Date: 2020-06-10 Impact factor: 14.136
Authors: Ligia L Castro; Jamil Z Kitoko; Debora G Xisto; Priscilla C Olsen; Herbert L M Guedes; Marcelo M Morales; Miquéias Lopes-Pacheco; Fernanda F Cruz; Patricia R M Rocco Journal: Stem Cells Transl Med Date: 2019-11-20 Impact factor: 6.940