Stem Cell Conditioned Medium Improves Acute Lung Injury in Mice: In Vivo Evidence for Stem Cell Paracrine

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Stem Cell Conditioned Medium Improves Acute Lung Injury in 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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13 Nov 2012 Recommended

Matthias Ochs
F1000 Physiology Hannover Medical School, Hannover, Germany.

Christian Mhlfeld
F1000 Physiology Hannover Medical School, Hannover, Germany.

Follow Interesting Hypothesis, New Finding, Novel Drug Target DOI: 10.3410/f.717961851.793464478

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This study contains a number of well-designed experiments that provide clear evidence of a beneficial paracrine effect of mesenchymal stem cells (MSCs) in the setting of lipopolysaccharide (LPS)-induced acute lung injury in the 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. The authors of this paper provide a convincing argument for a paracrine action of MSCs mediated by effects on alveolar macrophages, which they describe as a 'wound healing/anti-inflammatory' phenotype. The in vivo studies involve the application of MSC conditioned medium, MSCs, fibroblast conditioned medium and fibroblasts in LPSinduced acute lung injury. Several parameters of lung injury were equally reduced by MSCs and MSC conditioned medium. The authors further show that the effects on macrophages are at least partially related to the action of insulin-like growth factor I produced by MSCs. Taken together, this study adds important information on the mechanisms involved in MSC effects in acute lung injury. Disclosures None declared
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Abstract:
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 or promote repair. Mesenchymal stem cells (MSCs) prevent lung injury in various experimental models, despite a low proportion of donor-derived cell engraftment, suggesting that MSCs exert their beneficial effects via paracrine mechanisms. We hypothesized that soluble factors secreted by MSCs promote the resolution of lung injury in part by modulating alveolar 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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Stem Cell Conditioned Medium Improves Acute Lung Injury in Mice: In Vivo Evidence for Stem Cell Paracrine Action. - F1000Prime

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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 enhanced expression 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, including insulin 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. MSCCdM promotes the resolution of LPS-induced lung injury by attenuating lung inflammation and promoting a wound healing/anti-inflammatory M2 macrophage phenotype in part via IGF-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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