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EARLの医学ノート

drmagician.exblog.jp

敗血症をメインとした集中治療,感染症,呼吸器のノート.Stop Sepsis, Save Lives.

敗血症と間葉系幹細胞

■講演会ではちらっとだけ喋ることはあるが,本ブログの敗血症カテゴリのまとめでは間葉系幹細胞には全く触れていない(「敗血症講演会概要」ではちょっとだけ記載).小生自身が再生医療を全然知らないこと,まだまだ臨床応用されないことから文献も読んでいない.簡便に入手できて点滴投与が可能,臓器損傷部位に集積し(Engraftment effect),抗炎症効果を有する(Anti-inflammatory effect)ことだけは知っているが,ちょっとだけとはいえ,何も知らずに喋るのもなんなので2010年のブルージャーナルを拝読.近い将来,敗血症で臓器不全が残ってもMSCs投与で全て改善という治療法が可能になるのか?

■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.
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by DrMagicianEARL | 2012-04-24 17:14 | 敗血症 | Comments(0)

by DrMagicianEARL