Winn-funded Research:
Feline asthma, a lower airway inflammatory disease caused by an allergic response, has many similarities with human asthma. The hallmark features consist of airway inflammation, airway hyperresponsiveness, and irreversible airway remodeling. Traditional therapy usually includes use of glucocorticoids and bronchodilators. Glucocorticoids attenuate airway inflammation and bronchodilators tame down the airway hyperresponsiveness. Neither one reverses the abnormal allergic response, nor do they always prevent airway remodeling. It is airway remodeling that causes long-term declines in lung function in asthmatic patients.
Many asthmatic humans and cats respond well to glucocorticoids and bronchodilators; however, some asthmatics are refractory to treatment. In addition, glucocorticoids are not necessarily innocuous and could be contraindicated when certain other concurrent diseases, such as diabetes mellitus and heart disease. Since traditional therapy using glucocorticoids and bronchodilators might be inadequate or contraindicated, ‘novel treatments’ are needed. In particular, therapies that can address the airway remodeling would be highly desirable.
Dr. Carol Reinero and associates at the College of Veterinary Medicine at the University of Missouri investigated the use of adipose-derived mesenchymal stem cell (MSC) therapy in treating cats with chronic allergic asthma. Therapeutic benefit of stem cells was previously shown in murine models to switch from a TH2 to a TH1 phenotypic immune response, decrease eosinophilia in bronchoalveolar lavage (BALF), blunted airway hyperresponsiveness, and improved pulmonary histologic scores. However, these benefits did not bear out in human asthma clinical trials, possibly due to murine asthma models not be similar to human asthma as is the case for spontaneous feline asthma.
Nine cats with Bermuda grass allergen-induced chronic asthma were treated with six intravenous infusion of MSCs or placebo and longitudinally evaluated over a 1 year for airway inflammation, airway hyperresponsiveness, and airway remodeling1. Various methodologies were used to assess the cats, including BALF cytology, airflow limitation clinical scoring and ventilator-acquired pulmonary mechanics, thoracic computed tomographic (CT) scans, analysis of BGA-specific IgE in serum and BALF, and evaluating TH2/TH1 proliferation and modulation by measuring induction of immunosuppressive cytokine, interleukin (IL) – 10.
MSC therapy failed to decrease airway inflammation nor did it attenuate airway hyperresponsiveness in response to allergen challenge. There was no significant affect on allergen-specifc IgE, IL-10, or in CD4+ T lymphocyte proliferation in MSC-treated and placebo-treated cats. However, MSC therapy did reduce airway remodeling. Benefits regarding airway remodeling were not evident until 6 months after the last MCS infusion. Longitudinal evaluation of hallmark asthmatic features was possible in this study and demonstrated that reduction of remodeling was not permanent which holds relevance for future studies to determine how often dosing of MSCs might be necessary. [GO]
1 While sensitized cats display airway eosinophilia, hyperresponsivenness, and remodeling, only some are clinically symptomatic after allergen aerosol challenges, otherwise, they not clinically symptomatic for asthma and were adopted out to private homes after the study period.