Abstract
BackgroundData obtained in both animal models and clinical trials suggest that cell-based therapies represent a potential therapeutic strategy for lung repair and remodeling. Recently, new therapeutic approaches based on the use of stem cell derivatives (e.g., conditioned medium (CM) and microvesicles (MVs)) to regenerate tissues and improve their functions were proposed. The aim of this study was to investigate the immunomodulatory effects of equine amniotic mesenchymal cell derivatives on lipopolysaccharide (LPS)-induced cytokine production in equine alveolar macrophages, which may be beneficial in lung inflammatory disorders such as recurrent airway obstruction (RAO) in horses. RAO shares many features with human asthma, including an increased number of cells expressing mRNA for interleukin (IL)-4 and IL-5 and a decreased expression of IFN-γ in bronchoalveolar lavage fluid (BALF) of affected horses.MethodsThe release of TNF-α, IL-6, and TGF-β1 at different time points (1, 24, 48, and 72 h) was measured in equine alveolar macrophages stimulated or not with LPS (10 and 100 ng/mL) in the presence or absence of 10 % CM or 50 × 106 MVs/mL.Cytokines were measured using commercially available ELISA kits. For multiple comparisons, analysis of variance was used with Tukey post-hoc test. Differences were considered significant at p ≤ 0.05.ResultsSignificant modulatory effects of CM on LPS-induced TNF-α release at 24 h, and of both CM and MVs on TNF-α release at 48 h were observed. A trend toward a modulatory effect of both CM and MVs on the release of TGF-β and possibly IL-6 was visible over time.ConclusionsResults support the potential use of CM and MVs in lung regenerative medicine, especially in situations in which TGF-β may be detrimental, such as respiratory allergy. Further studies should evaluate the potential clinical applications of CM and MVs in equine lung diseases, such as RAO and other inflammatory disorders.
Highlights
Data obtained in both animal models and clinical trials suggest that cell-based therapies represent a potential therapeutic strategy for lung repair and remodeling
To explain the action of mesenchymal stem cells (MSCs), several paracrine mechanisms have been proposed for bone marrow-derived stem cell effects, including release of anti-inflammatory mediators such as interleukin (IL)-10, angiopoietin-1, and keratinocyte growth factor (KGF) that could modulate immune responses
Amniotic mesenchymal cell (AMC) observed at the early stages of culture were organized as three-dimensional clusters (Fig. 1b)
Summary
Data obtained in both animal models and clinical trials suggest that cell-based therapies represent a potential therapeutic strategy for lung repair and remodeling. New therapeutic approaches based on the use of stem cell derivatives (e.g., conditioned medium (CM) and microvesicles (MVs)) to regenerate tissues and improve their functions were proposed. Regenerative medicine is a new therapeutic approach based on the use of stem cells and their derivatives (e.g. conditioned medium (CM) and microvesicles (MVs)) to regenerate tissues and to improve their function, including lung diseases [1,2,3,4,5]. Several recent reports suggested that both systemic and intrapulmonary administration of bone marrow-derived mature stem cells in mice models of acute lung injury resulted in decreased mortality, improved alveolar fluid clearance, and attenuated inflammation and lung injury, despite minimal, if any, stem cell engraftment in the lung [1]. To explain the action of mesenchymal stem cells (MSCs), several paracrine mechanisms have been proposed for bone marrow-derived stem cell effects, including release of anti-inflammatory mediators such as interleukin (IL)-10, angiopoietin-1, and keratinocyte growth factor (KGF) that could modulate immune responses
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