IPSC- and mesenchymoangioblast-derived mesenchymal stem cells provide greater protection against experimental chronic allergic airways disease compared with a clinically used corticosteroid.

Abstract

The airway remodeling (AWR) associated with chronic allergic airways disease (AAD)/asthma contributes to irreversible airway obstruction. This study compared and combined the antiremodeling and other effects of induced pluripotent stem cell and mesenchymoangioblast-derived mesenchymal stem cells (MCA-MSCs) with the corticosteroid dexamethasone (Dex) in experimental chronic AAD/asthma. Female BALB/c mice subjected to 11 wk of ovalbumin (Ova)-induced chronic AAD were intranasally administered MCA-MSCs (1 × 106 cells/mouse; once weekly on wk 10 and 11), Dex (0.5 mg/ml; once daily for 2 wk), or both combined. MCA-MSC detection and changes in airway inflammation (AI), AWR, and airway hyperresponsiveness (AHR) were measured at the end of wk 11. Mice with chronic AAD had significant AI, goblet cell metaplasia, epithelial damage/thickening, aberrant TGF-β1 levels, subepithelial myofibroblast accumulation, airway/lung fibrosis, and AHR (all P < 0.001 vs. healthy controls). MCA-MSCs were detected in the lungs up to 5-7 d postadministration and demonstrated modest anti-inflammatory but striking antifibrotic effects against Ova-induced AAD, effectively decreasing AHR by 70-75% (all P < 0.05 vs. Ova alone). In comparison, Dex predominantly demonstrated anti-inflammatory effects, decreasing AHR by ∼30%. Combining MCA-MSCs with Dex provided equivalent protection to that offered by either therapy alone. MCA-MSCs reduce chronic AAD-induced AWR and AHR to a greater extent than Dex and may act as a suitable adjunct therapy to corticosteroid treatment of asthma.-Royce, S. G., Mao, W., Lim, R., Kelly, K., Samuel, C. S. iPSC- and mesenchymoangioblast-derived mesenchymal stem cells provide greater protection against experimental chronic allergic airways disease compared with a clinically used corticosteroid.