Mesenchymal stem cells reduce inflammation while enhancing bacterial clearance and improving survival in sepsis.

By S. Mei, J. Haitsma, C. D. dos Santos, Yupu P Deng, P. Lai, Arthur S Slutsky, W. Liles, D. Stewart. American Journal of Respiratory and Critical Care Medicine, 2010

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RATIONALE Sepsis refers to the clinical syndrome of severe systemic inflammation precipitated by infection. Despite appropriate antimicrobial therapy, sepsis-related morbidity and mortality remain intractable problems in critically ill patients. Moreover, there is no specific treatment strategy for the syndrome of sepsis-induced multiple organ dysfunction. OBJECTIVES We hypothesized that mesenchymal stem cells (MSCs), which have been shown to have immunomodulatory properties, would reduce sepsis-induced inflammation and improve survival in a polymicrobial model of sepsis. METHODS Sepsis was induced in C57Bl/6J mice by cecal ligation and puncture (CLP), followed 6 hours later by an intravenous injection of MSCs or saline. Twenty-eight hours after CLP, plasma, bronchoalveolar lavage fluid and tissues were collected for analyses. Longer-term studies were performed with antibiotic coadministration to assess the effect of MSCs on survival. MEASUREMENTS AND MAIN RESULTS MSC treatment significantly reduced mortality in septic mice receiving appropriate antimicrobial therapy. MSCs alone reduced systemic and pulmonary cytokine levels in mice with CLP-induced sepsis, preventing acute lung injury and organ dysfunction, despite the low levels of cell persistence. Microarray data highlighted an overall down-regulation of inflammation and inflammation-related genes (such as IL-10, IL-6) and a shift toward up-regulation of genes involved in promoting phagocytosis and bacterial killing. Finally, bacterial clearance was significantly greater in MSC-treated mice, in part due to enhanced phagocytotic activity of the host immune cells. CONCLUSIONS These data demonstrate that MSCs have beneficial effects on experimental sepsis, possibly by paracrine mechanisms, and suggest that immunomodulatory cell therapy may be an effective adjunctive treatment to reduce sepsis-related morbidity and mortality.

Subfields: Genetics, Immunology, Surgery

View Paper: https://www.semanticscholar.org/paper/71d83f445f446fb4ce46cf07318ae5652b76872f

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Citations in the corpus

Safety of Cell Therapy with Mesenchymal Stromal Cells (SafeCell): A Systematic Review and Meta-Analysis of Clinical Trials (2012, background): “[2] There is a growing body of literature demonstrating the efficacy of MSC therapy in a variety of pre-clinical models, including acute lung injury, [3,4] septic shock, [5] and acute myocardial infarction.”
Antibacterial Effect of Human Mesenchymal Stem Cells Is Mediated in Part from Secretion of the Antimicrobial Peptide LL-37 (2010, background): “[23] showed that the improvement in bacterial clearance in MSC-treated septic mice following CLP could be in part explained by enhanced phagocytic activity of host immune cells, it is not known yet whether human BM-derived MSCs possess direct antimicrobial activity.”
Mesenchymal Stromal Cells Modulate Macrophages in Clinically Relevant Lung Injury Models by Extracellular Vesicle Mitochondrial Transfer (2017, background): “Am J Respir Crit Care Med 2013;187(7):751-760.”