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Stem Cell Res Ther. 2017 Jun 24;8(1):151. doi: 10.1186/s13287-017-0600-8.

Human adipose tissue mesenchymal stromal cells and their extracellular vesicles act differentially on lung mechanics and inflammation in experimental allergic asthma.

Author information

1
Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Avenida Carlos Chagas Filho, 373, Bloco G-014, Ilha do Fundão, 21941-902, Rio de Janeiro, RJ, Brazil.
2
Laboratory of Cellular and Molecular Physiology, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
3
Laboratory of Clinical Bacteriology and Immunology, Health Sciences Center, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
4
Program of Morphological Sciences, Biomedical Sciences Institute, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
5
Laboratory of Inflammation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, RJ, Brazil.
6
Department of Medicine, University of Vermont, College of Medicine, Burlington, VT, USA.
7
Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Avenida Carlos Chagas Filho, 373, Bloco G-014, Ilha do Fundão, 21941-902, Rio de Janeiro, RJ, Brazil. prmrocco@biof.ufrj.br.

Abstract

BACKGROUND:

Asthma is a chronic inflammatory disease that can be difficult to treat due to its complex pathophysiology. Most current drugs focus on controlling the inflammatory process, but are unable to revert the changes of tissue remodeling. Human mesenchymal stromal cells (MSCs) are effective at reducing inflammation and tissue remodeling; nevertheless, no study has evaluated the therapeutic effects of extracellular vesicles (EVs) obtained from human adipose tissue-derived MSCs (AD-MSC) on established airway remodeling in experimental allergic asthma.

METHODS:

C57BL/6 female mice were sensitized and challenged with ovalbumin (OVA). Control (CTRL) animals received saline solution using the same protocol. One day after the last challenge, each group received saline, 105 human AD-MSCs, or EVs (released by 105 AD-MSCs). Seven days after treatment, animals were anesthetized for lung function assessment and subsequently euthanized. Bronchoalveolar lavage fluid (BALF), lungs, thymus, and mediastinal lymph nodes were harvested for analysis of inflammation. Collagen fiber content of airways and lung parenchyma were also evaluated.

RESULTS:

In OVA animals, AD-MSCs and EVs acted differently on static lung elastance and on BALF regulatory T cells, CD3+CD4+ T cells, and pro-inflammatory mediators (interleukin [IL]-4, IL-5, IL-13, and eotaxin), but similarly reduced eosinophils in lung tissue, collagen fiber content in airways and lung parenchyma, levels of transforming growth factor-β in lung tissue, and CD3+CD4+ T cell counts in the thymus. No significant changes were observed in total cell count or percentage of CD3+CD4+ T cells in the mediastinal lymph nodes.

CONCLUSIONS:

In this immunocompetent mouse model of allergic asthma, human AD-MSCs and EVs effectively reduced eosinophil counts in lung tissue and BALF and modulated airway remodeling, but their effects on T cells differed in lung and thymus. EVs may hold promise for asthma; however, further studies are required to elucidate the different mechanisms of action of AD-MSCs versus their EVs.

KEYWORDS:

Asthma; Extracellular vesicles; Inflammation; Mesenchymal stromal cells; Remodeling

PMID:
28646903
PMCID:
PMC5482954
DOI:
10.1186/s13287-017-0600-8
[Indexed for MEDLINE]
Free PMC Article

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