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

Abstract：

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.

journal_name

Am J Respir Crit Care Med

journal_title

American journal of respiratory and critical care medicine

authors

Mei SH,Haitsma JJ,Dos Santos CC,Deng Y,Lai PF,Slutsky AS,Liles WC,Stewart DJ

doi

10.1164/rccm.201001-0010OC

subject

Has Abstract

pub_date

2010-10-15 00:00:00

pages

1047-57

issue

eissn

1073-449X

issn

1535-4970

pii

201001-0010OC

journal_volume

182

pub_type

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