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Long‐term evaluation of mesenchymal stem cell therapy in a feline model of chronic allergic asthma
Author(s) -
Trzil J. E.,
Masseau I.,
Webb T. L.,
Chang C.H.,
Dodam J. R.,
Cohn L. A.,
Liu H.,
Quimby J. M.,
Dow S. W.,
Reinero C. R.
Publication year - 2014
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.12411
Subject(s) - medicine , asthma , eosinophilia , bronchoalveolar lavage , immunology , immunoglobulin e , lung , mesenchymal stem cell , pathology , antibody
Summary Background Mesenchymal stem cells ( MSC s) decrease airway eosinophilia, airway hyperresponsiveness ( AHR ), and remodelling in murine models of acutely induced asthma. We hypothesized that MSC s would diminish these hallmark features in a chronic feline asthma model. Objective To document effects of allogeneic, adipose‐derived MSC s on airway inflammation, AHR , and remodelling over time and investigate mechanisms by which MSC s alter local and systemic immunologic responses in chronic experimental feline allergic asthma. Methods Cats with chronic, experimentally induced asthma received six intravenous infusions of MSC s (0.36–2.5 × 10E7 MSC s/infusion) or placebo bimonthly at the time of study enrollment. Cats were evaluated at baseline and longitudinally for 1 year. Outcome measures included: bronchoalveolar lavage fluid cytology to assess airway eosinophilia, pulmonary mechanics and clinical scoring to assess AHR , and thoracic computed tomographic ( CT ) scans to assess structural changes (airway remodelling). CT scans were evaluated using a scoring system for lung attenuation ( LA ) and bronchial wall thickening ( BWT ). To assess mechanisms of MSC action, immunologic assays including allergen‐specific IgE, cellular IL ‐10 production, and allergen‐specific lymphocyte proliferation were performed. Results There were no differences between treatment groups or over time with respect to airway eosinophilia or AHR . However, significantly lower LA and BWT scores were noted in CT images of MSC ‐treated animals compared to placebo‐treated cats at month 8 of the study ( LA P = 0.0311; BWT P = 0.0489). No differences were noted between groups in the immunologic assays. Conclusions and Clinical Relevance When administered after development of chronic allergic feline asthma, MSC s failed to reduce airway inflammation and AHR . However, repeated administration of MSC s at the start of study did reduce computed tomographic measures of airway remodelling by month 8, although the effect was not sustained at month 12. Further study of MSC therapy including repeated MSC administration is warranted to assess impact on remodelling in chronic asthma.