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Intranasal administration of mesenchymoangioblast‐derived mesenchymal stem cells abrogates airway fibrosis and airway hyperresponsiveness associated with chronic allergic airways disease
Author(s) -
Royce Simon G.,
Rele Siddharth,
Broughton Brad R. S.,
Kelly Kilian,
Samuel Chrishan S.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201700178r
Subject(s) - medicine , nasal administration , mesenchymal stem cell , ovalbumin , immunology , fibrosis , airway , goblet cell , bronchoalveolar lavage , lung , pathology , epithelium , immune system , anesthesia
Structural changes known as airway remodeling (AWR) characterize chronic/severe asthma and contribute to lung dysfunction. Thus, we assessed the in vivo efficacy of induced pluripotent stem cell and mesenchymoangioblast‐derived mesenchymal stem cells (MCA‐MSCs) on AWR in a murine model of chronic allergic airways disease (AAD)/asthma. Female Balb/c mice were subjected to a 9‐wk model of ovalbumin (Ova)‐induced chronic AAD and treated intravenously or intranasally with MCA‐MSCs from weeks 9 to 11. Changes in airway inflammation (AI), AWR, and airway hyperresponsiveness (AHR) were assessed. Ova‐injured mice presented with AI, goblet cell metaplasia, epithelial thickening, increased airway TGF‐β1 levels, subepithelial myofibroblast and collagen accumulation, total lung collagen concentration, and AHR (all P < 0.001 vs. uninjured control group). Apart from epithelial thickness, all other parameters measured were significantly, although not totally, decreased by intravenous delivery of MCA‐MSCs to Ova‐injured mice. In comparison, intranasal delivery of MCA‐MSCs to Ova‐injured mice significantly decreased all parameters measured (all P < 0.05 vs. Ova group) and, most notably, normalized aberrant airway TGF‐β1 levels, airway/lung fibrosis, and AHR to values measured in uninjured animals. MCA‐MSCs also increased collagen‐degrading gelatinase levels. Hence, direct delivery of MCA‐MSCs offers great therapeutic benefit for the AWR and AHR associated with chronic AAD.—Royce, S. G., Rele, S., Broughton, B. R. S., Kelly, K., Samuel, C. S. Intranasal administration of mesenchymoangioblast‐derived mesenchymal stem cells abrogates airway fibrosis and airway hyperresponsiveness associated with chronic allergic airways disease. FASEB J. 31, 4168–4178 (2017). www.fasebj.org —Royce, Simon G., Rele, Siddharth, Broughton, Brad R. S., Kelly, Kilian, Samuel, Chrishan S., Intranasal administration of mesenchymoangioblast‐derived mesenchymal stem cells abrogates airway fibrosis and airway hyperresponsiveness associated with chronic allergic airways disease. FASEB J. 31, 4168–4178 (2017)