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

Stem Cell Research & Therapy

Daniel Jay Weiss¹  Marcelo Marcos Morales²  Priscilla Christina Olsen³  Tatiana Paula Teixeira Ferreira⁴  Marco Aurélio Martins⁴  Patricia Rieken Macedo Rocco⁵  Ligia Lins de Castro⁵  Jamil Zola Kitoko⁵  Debora Gonçalves Xisto⁵  Fernanda Ferreira Cruz⁵  Patricia Albuquerque Garcia Redondo⁶ 

[1] Department of Medicine, University of Vermont, College of Medicine;Laboratory of Cellular and Molecular Physiology, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro;Laboratory of Clinical Bacteriology and Immunology, Health Sciences Center, Federal University of Rio de Janeiro;Laboratory of Inflammation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation;Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro;Program of Morphological Sciences, Biomedical Sciences Institute, Federal University of Rio de Janeiro;

关键词: Asthma;    Remodeling;    Mesenchymal stromal cells;    Extracellular vesicles;    Inflammation;   

DOI  :  10.1186/s13287-017-0600-8

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown