Mesenchymal stem cells regulate airway contractile tissue remodeling in murine experimental asthma

Abstract

Background: Mesenchymal stem cells may offer therapeutic potential for asthma due to their immunomodulatory properties and host tolerability, yet prior evidence suggests that bloodborne progenitor cells may participate in airway remodeling. Here, we tested whether mesenchymal stem cells administered as anti-inflammatory therapy may favor airway remodeling and therefore be detrimental. Methods: Adipose tissue-derived mesenchymal stem cells were retrovirally transduced to express green fluorescent protein and intravenously injected into mice with established experimental asthma induced by repeat intranasal house dust mite extract. Controls were house dust mite-instilled animals receiving intravenous vehicle or phosphate-buffered saline-instilled animals receiving mesenchymal stem cells. Data on lung function, airway inflammation, and remodeling were collected at 72 h after injection or after 2 weeks of additional intranasal challenge. Results: The mesenchymal stem cells homed to the lungs and rapidly downregulated airway inflammation in association with raised T-helper-1 lung cytokines, but such effect declined under sustained allergen challenge despite a persistent presence of mesenchymal stem cells. Conversely, airway hyperresponsiveness and contractile tissue underwent a late reduction regardless of continuous pathogenic stimuli and inflammatory rebound. Tracking of green fluorescent protein did not show mesenchymal stem cell integration or differentiation in airway wall tissues. Conclusions: Therapeutic mesenchymal stem cell infusion in murine experimental asthma is free of unwanted pro-remodeling effects and ameliorates airway hyper-responsiveness and contractile tissue remodeling. These outcomes support furthering the development of mesenchymal stem cell-based asthma therapies, although caution and solid preclinical data building are warranted.