Abstract
BackgroundAsthma 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.MethodsC57BL/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.ResultsIn 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.ConclusionsIn 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.
Highlights
Asthma is a chronic inflammatory disease that can be difficult to treat due to its complex pathophysiology
In a mouse model of severe asthma induced by Aspergillus hyphal extract, systemically administered extracellular vesicles (EVs) derived from human bone marrow-derived mesenchymal stromal cells (MSCs) were effective as the MSCs themselves in ameliorating airway hyperresponsiveness, histologic inflammation, and inflammatory markers in bronchoalveolar lavage fluid (BALF); airway remodeling was not evaluated [11]
The present study comparatively assessed effects of systemic administration of human adipose tissue-derived MSCs (AD-MSC) versus EVs derived from the ADMSCs in a model of severe ovalbumin-induced allergic inflammation and airway remodeling in immunocompetent mice
Summary
Asthma is a chronic inflammatory disease that can be difficult to treat due to its complex pathophysiology. Human mesenchymal stromal cells (MSCs) are effective at reducing inflammation and tissue remodeling; 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. Most patients with asthma achieve disease control with a combination of corticosteroids and long-acting β2-adrenoceptor agonists [1] These drugs minimize inflammation and slow accompanying airway remodeling. To date, no study has evaluated the therapeutic potential of EVs derived from any source of MSCs once airway remodeling is already established Within this context, the present study comparatively assessed effects of systemic administration of human AD-MSCs versus EVs derived from the ADMSCs in a model of severe ovalbumin-induced allergic inflammation and airway remodeling in immunocompetent mice
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