Mesenchymal stem cells regulate airway contractile tissue remodeling in murine experimental asthma
Por:
Marinas-Pardo, L, Mirones, I, Amor-Carro, O, Fraga-Iriso, R, Lema-Costa, B, Cubillo, I, Milla, MAR, Garcia-Castro, J, Ramos-Barbon, D
Publicada:
1 jun 2014
Resumen:
BackgroundMesenchymal stem cells may offer therapeutic potential for asthma due to their immunomodulatory properties and host tolerability, yet prior evidence suggests that bloodborne progenitor cells may participate in airway remodeling. Here, we tested whether mesenchymal stem cells administered as anti-inflammatory therapy may favor airway remodeling and therefore be detrimental.
MethodsAdipose tissue-derived mesenchymal stem cells were retrovirally transduced to express green fluorescent protein and intravenously injected into mice with established experimental asthma induced by repeat intranasal house dust mite extract. Controls were house dust mite-instilled animals receiving intravenous vehicle or phosphate-buffered saline-instilled animals receiving mesenchymal stem cells. Data on lung function, airway inflammation, and remodeling were collected at 72h after injection or after 2weeks of additional intranasal challenge.
ResultsThe mesenchymal stem cells homed to the lungs and rapidly downregulated airway inflammation in association with raised T-helper-1 lung cytokines, but such effect declined under sustained allergen challenge despite a persistent presence of mesenchymal stem cells. Conversely, airway hyperresponsiveness and contractile tissue underwent a late reduction regardless of continuous pathogenic stimuli and inflammatory rebound. Tracking of green fluorescent protein did not show mesenchymal stem cell integration or differentiation in airway wall tissues.
ConclusionsTherapeutic mesenchymal stem cell infusion in murine experimental asthma is free of unwanted pro-remodeling effects and ameliorates airway hyper-responsiveness and contractile tissue remodeling. These outcomes support furthering the development of mesenchymal stem cell-based asthma therapies, although caution and solid preclinical data building are warranted.
Filiaciones:
Marinas-Pardo, L:
Complexo Hosp Univ, Resp Res Unit, Inst Invest Biomed A Coruna INIBIC, La Coruna, Spain
Inst Salud Carlos III, Cellular Biotechnol Unit, Madrid, Spain
Mirones, I:
Inst Salud Carlos III, Cellular Biotechnol Unit, Madrid, Spain
Amor-Carro, O:
Complexo Hosp Univ, Resp Res Unit, Inst Invest Biomed A Coruna INIBIC, La Coruna, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Resp Dept, E-08193 Barcelona, Spain
Fraga-Iriso, R:
Complexo Hosp Univ, Resp Res Unit, Inst Invest Biomed A Coruna INIBIC, La Coruna, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Resp Dept, E-08193 Barcelona, Spain
Lema-Costa, B:
Complexo Hosp Univ, Resp Res Unit, Inst Invest Biomed A Coruna INIBIC, La Coruna, Spain
Cubillo, I:
Inst Salud Carlos III, Cellular Biotechnol Unit, Madrid, Spain
Milla, MAR:
Inst Salud Carlos III, Cellular Biotechnol Unit, Madrid, Spain
Garcia-Castro, J:
Inst Salud Carlos III, Cellular Biotechnol Unit, Madrid, Spain
Ramos-Barbon, D:
Complexo Hosp Univ, Resp Res Unit, Inst Invest Biomed A Coruna INIBIC, La Coruna, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Resp Dept, E-08193 Barcelona, Spain
McGill Univ, Meakins Christie Labs, Dept Med, Montreal, PQ, Canada
Green Published, Hybrid Gold
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