Current asthma therapies primarily target airway inflammation (AI) and suppress episodes of airway hyperresponsiveness (AHR) but fail to treat airway remodelling (AWR), which can develop independently of AI and contribute to irreversible airway obstruction. This study compared the anti-remodelling and therapeutic efficacy of human bone marrow-derived mesenchymal stem cells (MSCs) to that of human amnion epithelial stem cells (AECs) in the setting of chronic allergic airways disease (AAD), in the absence or presence of an anti-fibrotic (serelaxin; RLX). Female Balb/c mice subjected to the 9-week model of ovalbumin (OVA)-induced chronic AAD, were either vehicle-treated (OVA alone) or treated with MSCs or AECs alone (intranasally (i.n)-administered with 1x106 cells once weekly), RLX alone (i.n-administered with 0.8mg/ml daily) or a combination of MSCs or AECs and RLX from weeks 9-11 (n=6/group). Measures of AI, AWR and AHR were then assessed. OVA alone exacerbated AI, epithelial damage/thickness, sub-epithelial extracellular matrix (ECM) and total collagen deposition, markers of collagen turnover and AHR compared to that in saline-treated counterparts (all p<0.01 vs saline-treated controls). RLX or AECs (but not MSCs) alone normalised epithelial thickness and partially diminished the OVA-induced fibrosis and AHR by ~40-50% (all p<0.05 vs OVA alone). Furthermore, the combination treatments normalised epithelial thickness, measures of fibrosis and AHR to that in normal mice, and significantly decreased AI. While AECs alone demonstrated greater protection against the AAD-induced AI, AWR and AHR, compared to that of MSCs alone, combining RLX with MSCs or AECs reversed airway fibrosis and AHR to an even greater extent.
- Airway remodeling
- Stem cells
- ©2016 The Author(s)
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