stem cell conditioned medium improves acute lung injury in mice_ in vivo evidence for stem cell...
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06/12/13 5:43 PMStem Cell Conditioned Medium Improves Acute Lung Injury in Mice: In Vivo Evidence for Stem Cell Paracrine Action. - F1000Prime
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DOI: 10.3410/f.717961851.793464478
This study contains a number of well-designed experiments that provide clear evidence of a beneficial paracrineeffect of mesenchymal stem cells (MSCs) in the setting of lipopolysaccharide (LPS)-induced acute lung injury inthe mouse.
The beneficial effect of MSCs in experimental models of acute lung injury has been documented in recent years.However, only recently have studies started to clarify the mechanisms of action of MSCs in lung pathology. Theauthors of this paper provide a convincing argument for a paracrine action of MSCs mediated by effects onalveolar macrophages, which they describe as a 'wound healing/anti-inflammatory' phenotype. The in vivo studiesinvolve the application of MSC conditioned medium, MSCs, fibroblast conditioned medium and fibroblasts in LPS-induced acute lung injury. Several parameters of lung injury were equally reduced by MSCs and MSC conditionedmedium. The authors further show that the effects on macrophages are at least partially related to the action ofinsulin-like growth factor I produced by MSCs. Taken together, this study adds important information on themechanisms involved in MSC effects in acute lung injury.
DisclosuresNone declared
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Stem Cell Conditioned Medium Improves Acute Lung Injuryin Mice: In Vivo Evidence for Stem Cell Paracrine Action.Ionescu L, Byrne RN, van Haaften T, Vadivel A, Alphonse RS, Rey-Parra GJ, Weissmann G, Hall A,Eaton F, Thebaud B.Am J Physiol Lung Cell Mol Physiol. 2012 Sep 28
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Mortality and morbidity of acute lung injury and acute respiratory distress syndrome (ALI/ARDS) remain high because of the lack of pharmacological therapies to prevent injury orpromote repair. Mesenchymal stem cells (MSCs) prevent lung injury in various experimental models, despite a low proportion of donor-derived cell engraftment, suggesting thatMSCs exert their beneficial effects via paracrine mechanisms. We hypothesized that soluble factors secreted by MSCs promote the resolution of lung injury in part by modulatingalveolar macrophage (AMs) function. We tested the therapeutic effect of MSC-derived conditioned medium (CdM) compared to whole MSCs, lung fibroblasts and fibroblast (Fib)-CdM. Intratracheal MSCs and MSC-CdM significantly attenuated lipopolysaccharide (LPS)-induced lung neutrophil influx, lung edema and lung injury as assessed by an established
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Matthias Ochs F1000 Physiology Hannover Medical School, Hannover,Germany.
Christian Mühlfeld F1000 Physiology Hannover Medical School, Hannover,Germany.
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06/12/13 5:43 PMStem Cell Conditioned Medium Improves Acute Lung Injury in Mice: In Vivo Evidence for Stem Cell Paracrine Action. - F1000Prime
Page 2 of 2http://f1000.com/prime/717961851
lung injury score. MSC-CdM increased arginase-1 activity and Ym1 expression in LPS-exposed AMs. In vivo, AMs from LPS-MSC and LPS-MSC CdM lungs had enhancedexpression of Ym1 and decreased expression of iNOS compared to untreated LPS mice. This suggests that MSC-CdM promotes alternative macrophage activation to an M2"healer" phenotype. Comparative multiplex analysis of MSC- and Fib-CdM demonstrated that MSC-CdM contained several factors that may confer therapeutic benefit, includinginsulin growth-like growth factor I (IGF-I). Recombinant IGF-I partially reproduced the lung protective effect of MSC-CdM. In summary, MSCs act through a paracrine activity. MSC-CdM promotes the resolution of LPS-induced lung injury by attenuating lung inflammation and promoting a wound healing/anti-inflammatory M2 macrophage phenotype in part viaIGF-I.
DOI: 10.1152/ajplung.00144.2011
PMID: 23023971
Abstract courtesy of PubMed: A service of the National Library of Medicine and the National Institutes of Health.
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