Suppression of allergic airway inflammation in a mouse model of asthma by exogenous mesenchymal stem cells

Abstract

Mesenchymal stem cells (MSCs) have significant immunomodulatory effects in the development of acute lung inflammation and fibrosis. However, it is still unclear as to whether MSCs could attenuate allergic airway inflammation in a mouse model of asthma. We firstly investigated whether exogenous MSCs can relocate to lung tissues in asthmatic mice and analyzed the chemotactic mechanism. Then, we evaluated the in vivo immunomodulatory effect of exogenous MSCs in asthma. MSCs (2 × 10(6)) were administered through the tail vein to mice one day before the first airway challenge. Migration of MSCs was evaluated by flow cytometry. The immunomodulatory effect of MSCs was evaluated by cell counting in bronchoalveolar lavage fluid (BALF), histology, mast cell degranulation, airway hyperreactivity and cytokine profile in BALF. Exogenous MSCs can migrate to sites of inflammation in asthmatic mice through a stromal cell-derived factor-1α/CXCR4-dependent mechanism. MSCs can protect mice against a range of allergic airway inflammatory pathologies, including the infiltration of inflammatory cells, mast cell degranulation and airway hyperreactivity partly via shifting to a T-helper 1 (Th1) from a Th2 immune response to allergens. So, immunotherapy based on MSCs may be a feasible, efficient therapy for asthma.

Mesenchymal Stromal Cells Mediate Aspergillus Hyphal Extract-Induced Allergic Airway Inflammation by Inhibition of the Th17 Signaling Pathway

“…We and others have found that in mouse models of mild Th2-eosinophilic mediated AAI, systemic administration of MSCs either during initial sensitization or during challenge significantly ameliorates both AHR and lung inflammation [27][28][29][30][31][32][33][34][35][36][37][38]. In the current study, we demonstrated that systemic MSC administration during challenge ameliorates AHR and lung inflammation in a more severe model of acute mixed Th2/Th17-mediated neutrophilic AAI induced by mucosal exposure to and challenge with adjuvant-free AHE.…”

“…With respect to asthma, MSCs have been demonstrated to ameliorate experimentally induced T helper cell (Th) type 2-mediated eosinophilic allergic airway inflammation (AAI) in mice [27][28][29][30][31][32][33][34][35][36][37][38]. Immunogens investigated in models include sensitization and challenge with ovalbumin, ragweed pollen, dust mite antigen, and toluene diisocyanate, and comparable effects have been observed with syngeneic, allogeneic, or xenogeneic MSC administration.…”

Stem cells in animal asthma models: a systematic review

“…One exception was the group treated before sensitization in the Sun et al [17] study. However, treatment with MSCs before sensitization did decrease BAL total cell count in the Kavanagh [25] and Goodwin [20] studies. The other exception was the recurrent inflammation group in the Lathrop [13] study [13].…”

“…No significant effect was seen in 2 studies, including the Lathrop et al study [9,13]. MSC treatment led to a significant decrease in BAL IL-13 levels in 3 studies [9,15,17] (P < 0.001 to P < 0.05), including with treatment after allergen challenge [15], whereas BAL IL-13 levels were already low in controls in 1 study [25] and there was no significant change in 5 studies [12,13,20,23,24]. One short-term study that reported on IL-9 levels in BAL found a reduction with MSC treatment (P < 0.05) [26].…”

“…All other studies reported improvement in lung histopathology in mice treated with MSCs, with the improvement described as great, marked or dramatic. Visually, improvements in airway inflammation [4,9,10,15,25,26], peribronchial and perivascular infiltration [9,12,13,16,19,26], epithelial lining thickening [4,15,22], subepithelial smooth muscle layer thickening [22], basement membrane thickening [22] and goblet cell hyperplasia and mucus production [4,9,15,16,24] were seen. These improvements were seen in studies in which MSCs were administered before sensitization [20,21], before [4,9,10,13,16,19,23,24,26,27] or after [12,14,15,22] allergen challenge.…”