tetano
Editor, Senior Moderator
Am J Physiol Lung Cell Mol Physiol. 2014 Jul 18. pii: ajplung.00110.2014. [Epub ahead of print]
Influenza causes prolonged disruption of the alveolar-capillary barrier in mice unresponsive to mesenchymal stem cell therapy.
Gotts JE1, Abbott J2, Matthay MA2.
Author information
Abstract
Viral pneumonia is a major cause of acute respiratory distress syndrome (ARDS). Anti-inflammatory therapies for viral-induced lung injury show promise in preclinical models. Mesenchymal stem/stromal cells (MSCs) are multipotent, self-renewing cells that secrete anti-inflammatory cytokines and epithelial and endothelial growth factors. We inoculated mice intranasally with influenza A (murine-adapted PR8) or PBS, and sacrificed at multiple time points after infection for measures of lung injury and viral load. We report that influenza induces marked, long-lasting dysfunction of the alveolar-capillary barrier peaking at one week but lasting longer than 3 weeks post-infection. Weight loss, commonly employed as a criterion for euthanasia (and hence "survival") was found to be poorly predictive of the severity of lung injury at its peak; rather, persistent weight loss 11 days post-infection identified mice with impaired injury resolution. Murine and human bone-marrow derived MSCs (obtained from the NIH repository) were then administered intravenously during the rapid phase of injury progression. Murine MSCs (mMSCs) given twice 24 hours apart failed to improve weight loss, lung water, BAL inflammation, or histology. However, mMSCs prevented influenza-induced thrombocytosis and caused a modest reduction in lung viral load at day 7. Human MSCs administered intravenously showed a similar lack of efficacy. The results demonstrate that the influenza murine model bears important similarities to the slow resolution of ARDS in patients. Despite their potent therapeutic effects in many models of acute inflammation and lung injury, MSCs do not improve influenza-mediated lung injury in mice.
Copyright ? 2014, American Journal of Physiology - Lung Cellular and Molecular Physiology.
KEYWORDS:
ARDS; Acute lung injury; Mesenchymal stem cells; Pneumonia; Pulmonary edema
PMID:
25038188
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25038188
Influenza causes prolonged disruption of the alveolar-capillary barrier in mice unresponsive to mesenchymal stem cell therapy.
Gotts JE1, Abbott J2, Matthay MA2.
Author information
Abstract
Viral pneumonia is a major cause of acute respiratory distress syndrome (ARDS). Anti-inflammatory therapies for viral-induced lung injury show promise in preclinical models. Mesenchymal stem/stromal cells (MSCs) are multipotent, self-renewing cells that secrete anti-inflammatory cytokines and epithelial and endothelial growth factors. We inoculated mice intranasally with influenza A (murine-adapted PR8) or PBS, and sacrificed at multiple time points after infection for measures of lung injury and viral load. We report that influenza induces marked, long-lasting dysfunction of the alveolar-capillary barrier peaking at one week but lasting longer than 3 weeks post-infection. Weight loss, commonly employed as a criterion for euthanasia (and hence "survival") was found to be poorly predictive of the severity of lung injury at its peak; rather, persistent weight loss 11 days post-infection identified mice with impaired injury resolution. Murine and human bone-marrow derived MSCs (obtained from the NIH repository) were then administered intravenously during the rapid phase of injury progression. Murine MSCs (mMSCs) given twice 24 hours apart failed to improve weight loss, lung water, BAL inflammation, or histology. However, mMSCs prevented influenza-induced thrombocytosis and caused a modest reduction in lung viral load at day 7. Human MSCs administered intravenously showed a similar lack of efficacy. The results demonstrate that the influenza murine model bears important similarities to the slow resolution of ARDS in patients. Despite their potent therapeutic effects in many models of acute inflammation and lung injury, MSCs do not improve influenza-mediated lung injury in mice.
Copyright ? 2014, American Journal of Physiology - Lung Cellular and Molecular Physiology.
KEYWORDS:
ARDS; Acute lung injury; Mesenchymal stem cells; Pneumonia; Pulmonary edema
PMID:
25038188
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25038188