Abstract:
:Occupational asthma (OA) is characterized by allergic airway inflammation and hyperresponsiveness, leading to progressive airway remodeling and a concomitant decline in lung function. The management of OA remains suboptimal in clinical practice. Thus, establishing effective therapies might overcome the natural history of the disease. We evaluated the ability of human adipose-tissue-derived mesenchymal stem cells (hASCs), either unmodified or engineered to secrete the IL-33 decoy receptor sST2, to attenuate the inflammatory and respiratory symptoms in a previously validated mouse model of OA to ammonium persulfate (AP). Twenty-four hours after a dermal AP sensitization and intranasal challenge regimen, the animals received intravenously 1 × 10(6) cells (either hASCs or hASCs overexpressing sST2) or saline and were analyzed at 1, 3, and 6 days after treatment. The infused hASCs induced an anti-inflammatory and restorative program upon reaching the AP-injured, asthmatic lungs, leading to early reduction of neutrophilic inflammation and total IgE production, preserved alveolar architecture with nearly absent lymphoplasmacytic infiltrates, negligible smooth muscle hyperplasia/hypertrophy in the peribronchiolar areas, and baseline airway hyperreactivity (AHR) to methacholine. Local sST2 overexpression barely increased the substantial efficacy displayed by unmodified hASCs. Thus, hASCs may represent a viable multiaction therapeutic capable to adequately respond to the AP-injured lung environment by resolving inflammation, tissue remodeling, and bronchial hyperresponsiveness typical of OA.
journal_name
Stem Cells Devjournal_title
Stem cells and developmentauthors
Martínez-González I,Cruz MJ,Moreno R,Morell F,Muñoz X,Aran JMdoi
10.1089/scd.2013.0616subject
Has Abstractpub_date
2014-10-01 00:00:00pages
2352-63issue
19eissn
1547-3287issn
1557-8534journal_volume
23pub_type
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journal_title:Stem cells and development
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journal_title:Stem cells and development
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journal_title:Stem cells and development
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journal_title:Stem cells and development
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journal_title:Stem cells and development
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journal_title:Stem cells and development
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journal_title:Stem cells and development
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journal_title:Stem cells and development
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