Intravenous adipose-derived mesenchymal stem cell therapy for the treatment of feline asthma: a pilot study.

Abstract

OBJECTIVES: The aim of this study was to evaluate the feasibility and efficacy of serially administered adipose-derived mesenchymal stem cells (MSCs) in an experimental feline asthma model. METHODS: Allergic asthma was acutely induced with Bermuda grass allergen in six purpose-bred cats. Five intravenous infusions of allogeneic MSCs (n = 4; MSC-treated) or saline (n = 2; placebo-treated) were administered over the first 130 days after asthma induction. Infusions contained 2 &#xd7; 10, 4 &#xd7; 10, 4.7 &#xd7; 10, 1 &#xd7; 10and 1 &#xd7; 10cryopreserved MSCs/cat. For thoracic imaging additional cats were enrolled as control groups: four untreated, experimentally asthmatic cats (combined with placebo-treated cats), and six healthy, non-asthmatic cats. Outcome measures included airway eosinophilia, pulmonary mechanics, thoracic computed tomography and several immunologic assays. RESULTS: Cats were assessed for 9 months after treatment. At early points, airway eosinophil percentage was not affected by MSC administration (post-treatment average of days 12, 26, 47, 108 and 133 in MSC-treated cats was 41 &#xb1; 15% and in placebo-treated cats it was 34 &#xb1; 16%). By month 9, eosinophil percentages in all MSC-treated cats decreased to normal reference intervals (MSC-treated 6%; placebo-treated 20%; normal <17%). Diminished airway hyper-responsiveness was noted in all MSC-treated compared with placebo-treated cats at day 133 (dose of methacholine to double baseline airway resistance: MSC-treated median 22.9 mg/ml [range 6.4-64.0]; individual placebo-treated cats 1.1 and 5.0 mg/ml). Lung attenuation (mean &#xb1; SEM MSC-treated -865 &#xb1; 12 Hounsfield units [HU]; untreated asthmatics -820 &#xb1; 11 HU; P = 0.004) and bronchial wall thickening scores (median [interquartile range] MSC-treated 0 [0-1.5]; untreated asthmatic 11.6 [7.3-27.3]; P = 0.010) were significantly reduced in MSC-treated vs untreated asthmatic cats, consistent with decreased airway remodeling at month 9. No clear immunologic mechanisms by which MSCs act were determined. CONCLUSIONS AND RELEVANCE: MSCs may have a delayed effect in reducing airway inflammation, airway hyper-responsiveness and remodeling in experimentally induced asthmatic cats. Results warrant additional investigation of MSC therapy for asthma in cats.