Preventive effect of mesenchymal stem cells on luminal stricture after endoscopic submucosal dissection in the rectum

Research Project

Project/Area Number	16K09300
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	Katsurada Takehiko 北海道大学, 大学病院, 助教 (90507592)
Research Collaborator	Ohnishi Shunsuke
Project Period (FY)	2016-04-01 – 2019-03-31
Project Status	Completed (Fiscal Year 2018)
Budget Amount *help	¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000) Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000) Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords	間葉系幹細胞 / 大腸がん / 内視鏡的粘膜下層剥離術 / 術後狭窄 / 粘膜下層剥離術 / 消化管狭窄
Outline of Final Research Achievements	Mesenchymal stem cells (MSCs) are valuable in regenerative medicine, and MSC culture supernatant (MSC-CS) reportedly inhibits inflammation and fibrosis. We investigated whether the development of luminal stricture after circumferential endoscopic mucosal dissection (ESD) in the rectum could be prevented using MSC-CS enema. The degree of luminal stricture in the rectum was significantly lower in the MSC-CS group than in the control group. Furthermore, MSC-CS attenuated myofibroblast activation and hypertrophy of the muscularis propria and reduced inflammatory cell infiltration. Taken together, MSC-CS enema prevented luminal stricture after ESD, possibly by inhibiting the inflammatory reaction and fibrosis.
Academic Significance and Societal Importance of the Research Achievements	近年の内視鏡技術の発達により、大腸がんを内視鏡で広範囲に切除する方法(ESD)が普及しつつある。しかしながら、広範囲に切除すると大腸が狭窄して腸閉塞になるリスクがある。我々は、羊膜間葉系幹細胞から分泌される因子に着目し、この細胞の培養上清をESD後の部分に塗りつけることで狭窄を予防できることを動物実験で明らかにした。この方法が確立すれば、内視鏡医が術後の狭窄を危惧せずに広範囲に切除できる可能性がある。