Longitudinal evaluation of effects of adipose-derived mesenchymal stem cells in a model of feline allergic asthma

Abstract

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Asthma is characterized by airway inflammation, airway hyperresponsiveness (AHR), and structural changes in the lungs. Mesenchymal stem cells (MSCs) suppress hallmark characteristics of asthma in rodent models. We investigated effects of intravenous MSCs on airway inflammation, AHR, and remodeling in an experimental model of feline asthma. We hypothesized that a feline model would provide more relevant insights into MSC therapy for asthma compared to rodent models. Acutely- (phase I) and chronically-induced (phase II) experimental feline asthma was investigated. In phase I, 6 experimentally asthmatic cats received 5 IV infusions of allogeneic MSCs (n=4) or placebo (n=2) over 130 days. Six healthy and 4 untreated, experimentally asthmatic cats served as additional controls for thoracic CT. In phase II, 9 experimentally asthmatic cats received 6 bimonthly IV infusions of MSCs (n=5) or placebo (n=4). Outcomes included immunologic tests to assess the immune response/inflammation, pulmonary mechanics/clinical scoring to assess AHR, and thoracic CT to assess airway remodeling followed for 9 (phase I) or 12 (phase II) months. In phase I, decreased inflammation and AHR was noted, but not statistically evaluated. MSC-treated cats had significantly decreased CT parameters of remodeling at month 9. In phase II, inflammation and AHR were not significantly different between groups. CT indices of airway remodeling were significantly decreased at month 8, but not month 12 in MSC-treated cats. These studies suggest MSC infusions may decrease airway remodeling in acute and chronic asthma, but the effect is not sustained long-term. Further study is needed to investigate optimal dosing and safety.