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2021 Fiscal Year Final Research Report

New developments in regenerative therapy for critical illness: the role of novel inflammatory amplification mechanisms.

Research Project

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Project/Area Number 19H03760
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 55060:Emergency medicine-related
Research InstitutionOsaka University

Principal Investigator

Ogura Hiroshi  大阪大学, 医学系研究科, 准教授 (70301265)

Co-Investigator(Kenkyū-buntansha) 入澤 太郎  大阪大学, 医学部附属病院, 助教 (50379202)
清水 健太郎  大阪大学, 医学部附属病院, 助教 (60379203)
松本 寿健  大阪大学, 医学部附属病院, 特任助教(常勤) (70644003)
嶋津 岳士  大阪大学, 医学系研究科, 教授 (50196474)
吉矢 和久  大阪大学, 医学部附属病院, 助教 (40379201)
Project Period (FY) 2019-04-01 – 2022-03-31
Keywords再生 / 骨髄単核球細胞 / 細胞移植 / IL-6 / Arid-5 / 幹細胞 / グリコカリックス / 臓器障害
Outline of Final Research Achievements

In this study, we focused on Arid-5a signaling-related molecules as a novel mechanism of inflammation amplification during severe invasion and evaluated the effects of bone marrow-derived mononuclear cell transplantation in a model of multiple organ damage. The following results were obtained. 1) RNA expression of Arid-5a-related molecules (Arid-5a, Regnase-1, STAT3) on monocytes in sepsis patients, extracted from public databases, was significantly enhanced in parallel with inflammatory cytokines such as IL-6 2) Whole blood RNA sequencing analysis in septic patients revealed that RNA expression of Arid-5a, Regnase-1, STAT3 and IL-6 were all increased. 3) Bone marrow mononuclear cell transplantation suppresses elevated blood IL-6 and syndecan-1 levels and exerts endothelial cytoprotective effects in a model of sepsis.

Free Research Field

救急医学

Academic Significance and Societal Importance of the Research Achievements

本研究では、重度侵襲時における新規炎症増幅メカニズムとしてArid-5aシグナル関連分子に注目して評価した。敗血症患者におけるArid-5a関連分子(Arid-5a, Regnase-1, STAT3, IL-6)のRNA発現が増強すること、骨髄単核球細胞移植は多臓器障害モデルにおいて血中IL-6の上昇を抑え、内皮細胞保護作用を発揮することを明らかにした。以上の結果は、今まで不明であった敗血症など重度侵襲時の過剰炎症メカニズム、侵襲時幹細胞移植が有効性を発揮するメカニズムの解明に繋がる可能性を示しており、その学術的意義は大きい。また、今後の臨床応用に繋がれば、その社会的意義も大きい。

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Published: 2023-01-30  

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