Culture supernatant of adipose stem cells can ameliorate allergic airway inflammation via recruitment of CD4+CD25+Foxp3 T cells

Abstract

BackgroundIn a previous study, we demonstrated that intravenous administration of adipose tissue stem cells (ASCs) could significantly reduce allergic symptoms and suppress eosinophilic inflammation.MethodsTo evaluate the secretome of ASCs, we administrated culture supernatant of ASCs (ASC sup, which contains the ASC secretome) and uncultured fresh medium (con sup) into a mouse model of allergic airway inflammation. Subsequently we observed the mice for signs of inflammation and investigated Th1-, Th2-, and Treg-related cytokine levels as well as recruitment of Treg cells into the airway.ResultsWe found that ASC sup could ameliorate allergic airway inflammation in this model; the value of airway hyperresponsiveness, and the occurrence of inflammatory cell infiltration in the lung, as well as the number of eosinophils, and goblet cells in the lung epithelium were all significantly decreased by ASC sup treatment. In addition, ASC sup treatment significantly decreased the levels of IL-4, IL-5, and IL-13 in the bronchial alveolar lavage fluid and in culture medium of lung-draining lymph node cells of the animal model of acute asthma. We detected numerous CTLA-4 and Foxp3-expressing cells in the lung after ASC sup treatment. ASC sup was found to have a higher concentration of IL-10 and TGF-β compared to con sup.ConclusionsStem cells have powerful potential for therapeutic functions in various diseases, but they also have many drawbacks. In this study, we found strong immunosuppressive ability of ASC sup in an allergic airway mouse model. It may be possible to use ASC sup for treatment of many immunological diseases in the near future.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-016-0462-5) contains supplementary material, which is available to authorized users.

Screening and Functional Pathway Analysis of Pulmonary Genes Associated with Suppression of Allergic Airway Inflammation by Adipose Stem Cell-Derived Extracellular Vesicles

“…ASCs: adipose stem cells; Bex2: brainexpressed X-linked 2; CON: control; EV: extracellular vesicle; Fpr1: formyl peptide receptor 1; Igfbp6: insulin-like growth factor binding protein 6; OVA: ovalbumin; PON1: paraoxonase 1; Scgb1c1: secretoglobin family 1C member 1. Stem Cells International cytokine production and induction of Treg expansion [19,22]. Furthermore, ASC-derived EVs have been shown to reduce static lung elastance and collagen fiber deposition in lung parenchyma and airways in experimental allergic asthma [29].…”

“…However, MSCs have several drawbacks including immune rejection, risk of aneuploidy, difficulty of handling, and tumorigenicity. Previous studies have shown that ASC-derived secretome-containing EVs, even without ASCs, ameliorate allergic airway inflammation through the suppression of Th2 cytokine production and induction of Treg expansion [ 19 , 22 ]. Furthermore, ASC-derived EVs have been shown to reduce static lung elastance and collagen fiber deposition in lung parenchyma and airways in experimental allergic asthma [ 29 ].…”

“…Several recent studies have shown that T cell activation and proliferation are suppressed by the MSC culture supernatant (MSC sup) [16,17]. Accumulating evidence shows that administration of MSC sup or extracellular vesicles (EVs) released by MSCs is as effective as that of MSCs in suppressing allergic airway inflammation [18][19][20]. MSC-derived EVs were found to upregulate IL-10 and TGF-β1 from peripheral blood mononuclear cells of asthmatic patients, thereby promoting the proliferation and immune suppression capacity of Tregs [21].…”

Mesenchymal Stem Cells Enhance Pulmonary Antimicrobial Immunity and Prevent Following Bacterial Infection

“…Induction of Tregs is a pivotal mechanism by MSCs to exert immunosuppressive functions. Mechanisms involved in Treg induction by MSCs have been dug deeply [33,34]. The study by Akiyama et al showed that intravenous transfer of mouse bone marrow MSCs to naive mice induced T cell apoptosis in peripheral blood and bone marrow.…”

Autologous Adipose-Derived Stem Cells Reduce Burn-Induced Neuropathic Pain in a Rat Model

“…However, the mechanisms of these effects remain to be clarified. Several studies have observed anti-inflammation effects after the transplantation of adipose-derived stem cells (ASCs) in vitro and in vivo, with increased interleukin (IL)-10 and suppression of the NFκB signaling pathway [ 10 , 11 , 12 , 13 , 14 , 15 ]. Two of these studies also demonstrated anti-neuroinflammation effects [ 13 , 14 ].…”