Regenerative therapy following severe insults: Establishment of cell transplantation and elucidation of immunologic response

• Project/Area Number: 25253096
• Research Category: Grant-in-Aid for Scientific Research (A)
• 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(研究院), 准教授 (70301265)
• Co-Investigator(Kenkyū-buntansha): YOSHIYA KAZUHISA 大阪大学, 医学部附属病院, 助教 (40379201) ; SHIMAZU TAKESHI 大阪大学, 医学系研究科, 教授 (50196474) ; MATSUMOTO NAOYA 大阪大学, 医学系研究科, 招へい教員 (50359808) ; IRISAWA TARO 大阪大学, 医学系研究科, 特任助教 (50379202)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥45,110,000 (Direct Cost: ¥34,700,000、Indirect Cost: ¥10,410,000); Fiscal Year 2015: ¥13,000,000 (Direct Cost: ¥10,000,000、Indirect Cost: ¥3,000,000); Fiscal Year 2014: ¥13,000,000 (Direct Cost: ¥10,000,000、Indirect Cost: ¥3,000,000); Fiscal Year 2013: ¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000)
• Keywords: 侵襲 / 再生 / 血管内皮 / 細胞移植 / 腸管上皮幹細胞 / 免疫反応 / 骨髄単核球細胞 / RAGE / 免疫 / 炎症 / 幹細胞 / 腸管 / 敗血症 / 治療 / 骨髄間質細胞 / 多臓器障害

Outline of Final Research Achievements

The objectives of this study were to evaluate the regenerative/ immunological response after severe insults and to examine the effects of intravascular transplantation of stem cells. (Study 1) We examined soluble RAGE in patients with sepsis and found its association with endothelial injury and organ damage. (Study 2) In a mouse model of peritonitis, the expression of Lgr5, a marker of intestinal epithelial stem cell, was suppressed, showing the stem cell dysfunction in the gut. (Study 3) We clarified that transplantation of bone marrow derived mononuclear cells exerted anti-inflammatory effects and improved the survival in a rat model of crush injury.

Research Products

• [Journal Article] The clinical significance of circulating soluble RAGE in patients with severe sepsis (2015)
  • Author(s): Hisatake Matsumoto, Naoya Matsumo, Hiroshi Ogura, Junya Shimazaki, Kazuma Yamakawa, Kouji Yamamoto, and Takeshi Shimazu
  • Journal Title: J Trauma Acute Care Surg. Volume: 78 Issue: 6 Pages: 1086-1094
  • DOI: 10.1097/ta.0000000000000651
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Enhanced Expression of Cell-Specific Surface Antigens on Endothelial Microparticles in Sepsis-Induced Disseminated Intravascular Coagulation. (2015)
  • Author(s): Matsumoto H, Yamakawa K, Ogura H, Koh T, Matsumoto N, Shimazu T.
  • Journal Title: Shock Volume: 43 Pages: 443-449
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Enhanced expression of aquaporin 9 in activated polymorphonuclear leukocytes in patients with systemic inflammatory response syndrome. (2014)
  • Author(s): Matsushima A, Ogura H, Koh T, Shimazu T, Sugimoto H.
  • Journal Title: Shock Volume: 42 Pages: 322-326
  • DOI: 10.3389/fmicb.2014.00583
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Serial change of C1 unhibitor in patinets with sepsis - a prospctive observathional study (2016)
  • Author(s): Tomoya Hirose, Hiroshi Ogura, Hiroki Takahashi, et al
  • Organizer: 第３６回International Symposium on Intensive Care and Emergency Medicine
  • Place of Presentation: Square Brussels Meeting Center（Brussels,Belgium)
  • Year and Date: 2016-03-15
• [Presentation] 重症病態における腸内細菌叢の変化と腸管内治療による予後改善の可能性 (2015)
  • Author(s): 小島将裕、清水健太郎、小倉裕司、他
  • Organizer: 第４３回日本救急医学会
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 2015-10-21
• [Presentation] クラッシュ症候群ラットモデルに対する抗RAGE抗体の治療効果 (2015)
  • Author(s): 松本寿健、松本直也、小倉裕司、他
  • Organizer: 第２９回日本外傷学会
  • Place of Presentation: 札幌コンベンションセンター
  • Year and Date: 2015-06-11
• [Presentation] Evaluation of endothelial microparticles in sepsis induced DIC treated with recombinant thrombomodulin (2015)
  • Author(s): 高橋弘毅、松本寿健、松本直也、小倉裕司、山川一馬、嶋津岳士
  • Organizer: Society of Critical Care Medicine 44th Congress
  • Place of Presentation: 米国 Phoenix Convention center
  • Year and Date: 2015-01-20
• [Presentation] Survival improvement by anti-RAGE antibody administration in a rat model of crush injury (2015)
  • Author(s): 松本寿健、松本直也、小倉裕司、島崎淳也、中川淳一郎、山川一馬、嶋津岳士
  • Organizer: Society of Critical Care Medicine 44th Congress
  • Place of Presentation: 米国 Phoenix Convention center
  • Year and Date: 2015-01-20
• [Presentation] 外傷による全身炎症とその制御：クラッシュ症候群モデルにおける検討 (2014)
  • Author(s): 中川淳一郎、松本寿健、松本直也、小倉裕司、島崎淳也、山川一馬、嶋津岳士
  • Organizer: 第42回日本救急医学会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2014-10-29
• [Presentation] 重症敗血症病態における新規免疫応答因子の評価 (2014)
  • Author(s): 松本寿健、松本直也、小倉裕司、山川一馬、康泰珍、嶋津岳士
  • Organizer: 第42回日本救急医学会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2014-10-28
• [Presentation] The clinical significance of circulating soluble RAGE in patients with severe sepsis (2014)
  • Author(s): 松本寿健、松本直也、小倉裕司、島崎淳也、山川一馬、嶋津岳士
  • Organizer: American Association for the Surgery of Trauma
  • Place of Presentation: 米国 Philadelphia Marriott Downtown
  • Year and Date: 2014-09-13
• [Presentation] The effect of bone marrow stromal cell transplantation on endothelial protection against a rodent model of sepsis
  • Author(s): 松本 直也
  • Organizer: 第7回 アジア救急医学会
  • Place of Presentation: 東京フォーラム
• [Presentation] SIRS病態の解明とその制御：細胞機能、免疫機能からみたアプローチ
  • Author(s): 小倉 裕司
  • Organizer: 第41回日本集中治療医学会
  • Place of Presentation: 京都国際会館
• [Presentation] Transplantation of bone marrow-derived mononuclear cells can improve the survival rate and suppress the inflammatory response in a rat crush injury model
  • Author(s): 中川 淳一郎
  • Organizer: 第34回International Symposium on Intensive Care and Emergency Medicine
  • Place of Presentation: ベルギー ブリュッセル
• [Presentation] 敗血症に対する新治療戦略：骨髄間質細胞移植による血管内皮細胞保護
  • Author(s): 松本 直也
  • Organizer: 第50回日本腹部救急医学会
  • Place of Presentation: 東京京王プラザホテル