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Unformatted text preview: of January 15, 2012 This information is current as 2007;179;1855-1863 J Immunol Serikov and Michael A. Matthay Naveen Gupta, Xiao Su, Boris Popov, Jae Woo Lee, Vladimir Endotoxin-Induced Acute Lung Injury in Mice Improves Survival and Attenuates Marrow-Derived Mesenchymal Stem Cells Intrapulmonary Delivery of Bone References http://www.jimmunol.org/content/179/3/1855.full.html#related-urls Article cited in: http://www.jimmunol.org/content/179/3/1855.full.html#ref-list-1 , 18 of which can be accessed free at: cites 35 articles This article Subscriptions http://www.jimmunol.org/subscriptions is online at The Journal of Immunology Information about subscribing to Permissions http://www.aai.org/ji/copyright.html Submit copyright permission requests at Email Alerts http://www.jimmunol.org/etoc/subscriptions.shtml/ Receive free email-alerts when new articles cite this article. Sign up at Print ISSN: 0022-1767 Online ISSN: 1550-6606. Immunologists, Inc. All rights reserved. by The American Association of Copyright ©2007 9650 Rockville Pike, Bethesda, MD 20814-3994. The American Association of Immunologists, Inc., is published twice each month by The Journal of Immunology o n J a n u a r y 1 5 , 2 1 2 w w w . j i m m u n o l . o r g D o w n l o a d e d f r o m Intrapulmonary Delivery of Bone Marrow-Derived Mesenchymal Stem Cells Improves Survival and Attenuates Endotoxin-Induced Acute Lung Injury in Mice 1 Naveen Gupta, 2 * Xiao Su,* Boris Popov, † Jae Woo Lee,* Vladimir Serikov, † and Michael A. Matthay* Recent in vivo and in vitro work suggests that mesenchymal stem cells (MSC) have anti-inflammatory properties. In this study, we tested the effect of administering MSC directly into the airspaces of the lung 4 h after the intrapulmonary administration of Escherichia coli endotoxin (5 mg/kg). MSC increased survival compared with PBS-treated control mice at 48 h (80 vs 42%; p < 0.01). There was also a significant decrease in excess lung water, a measure of pulmonary edema (145 50 vs 87 20 l; p < 0.01), and bronchoalveolar lavage protein, a measure of endothelial and alveolar epithelial permeability (3.1 0.4 vs 2.2 0.8 mg/ml; p < 0.01), in the MSC-treated mice. These protective effects were not replicated by the use of further controls including fibroblasts and apoptotic MSC. The beneficial effect of MSC was independent of the ability of the cells to engraft in the lung and was not related to clearance of the endotoxin by the MSC. MSC administration mediated a down-regulation of proinflammatory responses to endotoxin (reducing TNF- and MIP-2 in the bronchoalveolar lavage and plasma) while increasing the anti- inflammatory cytokine IL-10. In vitro coculture studies of MSC with alveolar macrophages provided evidence that the anti- inflammatory effect was paracrine and was not cell contact dependent. In conclusion, treatment with intrapulmonary MSC markedly decreases the severity of endotoxin-induced acute lung injury and improves survival in mice. The Journal of Immu-...
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