Asthma is a common lower airway disease affecting cats that is characterized by inflammation and constriction of the airways causing difficulty breathing. Long term, remodeling of the airways may cause a permanent decline in lung function and poor response to therapy. Currently, there is no approved therapy that is consistently able to slow or reverse this remodelling in cats. However, in rodent models of this disease, mesenchymal stem cells have been shown to slow or prevent airway remodeling.
The study objectives were to document long term decreases in airway inflammation, airflow limitation, and remodelling in cases of feline chronic allergic asthma after treatment with mesenchymal stem cells. This Winn grant funded the portion of the study that looked at the long term effects of adipose-derived mesenchymal stem cells (MSCs) on airway remodeling using CT scans. The investigators hypothesized that longitudinal evaluation of asthmatic cats administered intravenous allogeneic MSCs (e.g., stem cells from an unrelated feline donor) would demonstrate decreased airway remodeling compared with cats receiving placebo.
Changes in airway remodeling were assessed using thoracic computed tomographic (CT) scans at months 8 and 12 after initiation of stem cell infusions. Specifically, bronchial wall thickening and the overall density of the tissues (lung attenuation) were assessed. With asthma, an increase in the thickness of the lower airways and density of the tissues occurs due to infiltration of inflammatory cells and chronic scarring.
Interestingly, there was significant improvement in airway remodeling noted at month 8 in the cats receiving stem cell compared with placebo therapy. The MSC-treated cats had significantly less thickening of the walls of their lower airways. In addition, the density of the tissues in MSC-treated cats was significantly less than that observed in placebo-treated cats. This effect was not observed at month 12. Thus, the effect of MSC therapy is likely not sustained long term and repeated infusions over time may be needed. Overall, this study provides exciting evidence to indicate that MSC infusion may be beneficial in blunting the changes in airway remodeling noted in cats with chronic asthma.
Winn/Miller Trust grant report: Longitudinal evaluation of effects of mesenchymal stem cells in feline chronic allergic asthma: Phase II, $10,000; Carol Reinero, Comparative Internal Medicine Laboratory, University of Missouri
