敗血症と間葉系幹細胞
■間葉系幹細胞(MSCs:Mesenchymal Stem Cells)は循環器や神経系領域でその有用性が報告されていた.このMSCsを盲腸結紮穿刺(CLP:cecal ligation and puncture)による重症敗血症誘発マウスに移植投与を行った群と生食投与プラセボ群との比較studyが以下の文献である.結果として,炎症が抑制され,MODSも軽快し,予後改善効果が示されているものの,いまだその機序は解明されるに至っておらず,より有効な使用法などが今後発見される可能性がある.
Mei SH, Haitsma JJ, Dos Santos CC, Deng Y, Lai PF, Slutsky AS, Liles WC, Stewart DJ.
Mesenchymal stem cells reduce inflammation while enhancing bacterial clearance and improving survival in sepsis.
Am J Respir Crit Care Med. 2010 Oct 15;182(8):1047-57. Epub 2010 Jun 17.
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.