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

• 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
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); Fiscal Year 2018: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2017: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
• 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 / 侵襲 / 再生 / 長寿 / 敗血症 / 幹細胞移植 / 救急医学 / 炎症 / adiponectin / 免疫

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.

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。

Research Products

• [Journal Article] Bone marrow-derived mononuclear cell therapy can attenuate systemic inflammation in rat heatstroke. (2018)
  • Author(s): Umemura Yutaka, Ogura Hiroshi , Matsuura Hiroshi, et al.
  • Journal Title: Scand J Trauma Resusc Emerg Med. Volume: 26 Pages: 97-97
  • DOI: 10.1186/s13049-018-0566-2
  • Peer Reviewed
• [Presentation] 急性炎症病態に対する骨髄由来単核球細胞移植による侵襲反応制御 (2018)
  • Author(s): 梅村 穣、小倉 裕司、清水 健太郎、他
  • Organizer: 日本ショック学会
• [Presentation] Bone Marrow-Derived Mononuclear Cell Therapy Can Attenuate Systemic Inflammation in Rat Heatstroke. (2018)
  • Author(s): 梅村 穣
  • Organizer: 47th Critical Care Congress, Henry B. Gonzalez Convention Center, San Antonio, Texas, USA
  • Int'l Joint Research
• [Presentation] 急性炎症病態に対する骨髄由来単核球細胞移植による侵襲反応制御の可能性 (2017)
  • Author(s): 梅村 穣
  • Organizer: 第45回日本救急医学会総会・学術集会
• [Presentation] IMPAIRED ADIPONECTIN TRANSPORT CAPACITY IN LEUKOCYTES FROM CRITICALLY ILL PATIENTS (2016)
  • Author(s): Yutaka Umemura, MD,* Kentaro Shimizu, MD,* Hiroshi Ogura, MD,* Jinkoo Kang, MD,* Tomoaki Natsukawa, MD,† Taichin Koh MT, § Norikazu Maeda, MD,‡ Tohru Funahashi, MD,‡ Iichiro Shimomura, MD,‡ Takeshi Shimazu, MD*
  • Organizer: 75th annual meeting of American Association for the Surgery of Trauma
  • Place of Presentation: 米国ハワイ
  • Int'l Joint Research