Prevention of stricture formation after endoscopic submucosal dissection using mesenchymal stem cell culture supernatant

Research Project

Project/Area Number	17K09342
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Gastroenterology
Research Institution	Hokkaido University
Principal Investigator	Ono Shoko 北海道大学, 大学病院, 講師 (60431376)
Co-Investigator(Kenkyū-buntansha)	大西俊介北海道大学, 医学研究院, 准教授 (10443475)
Project Period (FY)	2017-04-01 – 2020-03-31
Project Status	Completed (Fiscal Year 2019)
Budget Amount *help	¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000) Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000) Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords	食道がん / 内視鏡的粘膜下層剥離術 / 食道狭窄 / 間葉系幹細胞 / 羊膜
Outline of Final Research Achievements	Endoscopic submucosal dissection (ESD) for esophageal cancer often causes postoperative stricture when more than three-quarters of the circumference of the esophagus is dissected. Mesenchymal stem cells are a valuable cell source in regenerative medicine, and conditioned medium (CM) obtained from mesenchymal stem cells reportedly inhibits inflammation. In this study, we evaluated whether CM could prevent esophageal stricture after ESD. In a pig model of esophageal stricture after ESD, CM gel prevented esophageal stricture formation by suppressing myofibroblast activation and fibrosis following the infiltration of neutrophils and macrophages in acute phase. Oral administration of CM gel would be a promising treatment for the prevention of post-ESD stricture. We are currently evaluating the effect of CM on the prevention of re-stricture after balloon dilation.
Academic Significance and Societal Importance of the Research Achievements	内視鏡で切除可能な早期食道がんについて、切除後の食道狭窄の予防が患者のQOLの維持に重要であり、新規治療法の開発がのぞまれている。本研究では、再生医療材料として注目されている羊膜由来間葉系幹細胞に着目し、その培養上清を飲むことで食道狭窄を予防できることをブタの実験で明らかにした。今後、培養上清に含まれる重要な因子を同定し、そのメカニズムについて明らかにして、臨床応用めざして準備を進めていく。