2018 Fiscal Year Final Research Report

A novel development of regenerative therapy following acute systemic inflammatory response syndrome: the effects of transplantation of bone marrow-derived mononuclear cells and new rejuvenation factor

Research Project

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Project/Area Number	16H05498
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Research Field	Emergency medicine
Research Institution	Osaka University
Principal Investigator	Ogura Hiroshi 大阪大学, 医学系研究科, 准教授 (70301265)
Co-Investigator(Kenkyū-buntansha)	吉矢和久大阪大学, 医学部附属病院, 助教 (40379201) 嶋津岳士大阪大学, 医学系研究科, 教授 (50196474) 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) 新谷歩大阪市立大学, 大学院医学研究科, 教授 (00724395)
Project Period (FY)	2016-04-01 – 2019-03-31
Keywords	全身性炎症反応 / 臓器障害 / 若返り因子 / GDF11 / 再生医療 / 幹細胞 / 細胞移植 / 骨髄単核球細胞
Outline of Final Research Achievements	Systemic inflammatory response syndrome (SIRS)following major insults often leads to multiple organ dysfunction syndrome. Bone marrow-derived mononuclear cells (BMMNCs) secrete anti-inflammatory proteins and have protective effects against acute inflammation. The objectives of this study were to evaluate the effects of GDF（growth differentiation factor）11, a new rejuvenation factor, on SIRS following sepsis, and to clarify the mechanism how BMMNCs attenuate SIRS induced by severe heatstroke or crush injury. In the results, GDF11 administration did not affect the survival in sepsis model. On the other hand, transplantation of BMMNCs significantly attenuated acute systemic inflammation and vascular endothelial injury, reduced organ dysfunction, and improved survival in heatstroke or crush injury model. Especially, transplantation of BMMNCs significantly suppressed the elevations in serum pro-inflammatory mediators. These findings may provide a possible therapeutic strategy against SIRS.
Free Research Field	救急医学、集中治療医学、外科学、侵襲学
Academic Significance and Societal Importance of the Research Achievements	全身性炎症反応は、種々の過大侵襲により引き起こされ、しばしば制御困難となる。本研究では、急性期全身炎症反応に対する新規若返り因子GDF11および骨髄単核球細胞移植の効果を評価した。本研究結果をもとに将来的には侵襲に伴う様々な全身性炎症反応患者への有効な細胞移植治療が確立でき、さらなる臨床応用につながれば、急性期重症病態患者、およびその家族の病苦を劇的に軽減し、医療経済の面でも社会に貢献することができる。