Development of drug eluting bioresorbable stents with antiplatelet effect and protection against hepatic ischemia and reperfusion injury: application to liver transplantation

• Project/Area Number: 15K10172
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Keio University
• Principal Investigator: OBARA HIDEAKI 慶應義塾大学, 医学部(信濃町), 准教授 (20276265)
• Co-Investigator(Kenkyū-buntansha): 松原 健太郎 慶應義塾大学, 医学部(信濃町), 助教 (70348671) ; 藤村 直樹 慶應義塾大学, 医学部(信濃町), 助教 (80445212)
• Research Collaborator: Hayashi Keita 慶應義塾大学, 医学部, 助教 (80770859) ; Hayashi Masanori 慶應義塾大学, 医学部, 助教 (20793475)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: 生体吸収 / ステント / 虚血再灌流障害 / 肝移植 / 生体吸収ステント / 門脈吻合 / 門脈 / ミニブタ / ラット / 肝虚血再灌流障害 / シロスタゾール

Outline of Final Research Achievements

Since it was difficult to prepare cilostazol (CZ) eluting bioresorbable stent, the effects of CZ administration in rat hepatic ischemia reperfusion model were examined. Improvement of liver function value and decrease of production of various cytokines was observed by administration of CZ. In the CZ administration group, the survival rate was also significantly improved, which showing an inhibitory effect of CZ on hepatic ischemia reperfusion injury. Next, a portal anastomosis model and a portal vein stent placement model were created using large animals (pigs). Following laparotomy under general anesthesia, the portal vein was exposed and the anterior wall was cut by 2/3 rounds. After that, primary suturing closure of that part was performed. A guide wire and a vascular sheath were inserted from the distal part of the suture site of portal vein, and the metallic stent was placed under fluoroscopy. Angiography confirmed that the stent was precisely placed at the suture site.

Research Products

• [Presentation] Comparison of vascular remodeling between the bioresorbable Poly-L-lactic acid scaffold and the metallic stent in porcine iliac artery (2017)
  • Author(s): Keita Hayashi, Hideaki Obara, Kentaro Matsubara, Yuki Kamiya, Masanori Hayashi, Yasuhiro Sekimoto, Yuko Kitagawa
  • Organizer: Asian Society for Vascular Surgery
  • Int'l Joint Research
• [Presentation] Pretreatment of cilostazol attenuates hepatic ischemia/reperfusion injury in rats (2016)
  • Author(s): Fujii T, Obara H, Matsubara K, Yagi H, Hibi T,Abe Y,Kitago M,Shinoda M,Itano O, Kitagawa Y
  • Organizer: 26th International Congress of The Transplantation Society(TTS2016)
  • Place of Presentation: Hong Kong
  • Year and Date: 2016-08-20
  • Int'l Joint Research
• [Presentation] Beneficial Effects Of Cilostazol On Ischemia/Reperfusion Injury In The Rat Liver (2015)
  • Author(s): Fujii T, Obara H, Matsubara K, Kitagawa Y
  • Organizer: Congress of the Asian Society of Transplantation (CAST)
  • Place of Presentation: Suntec Singapore Convention & Exhibition Centre (Singapore)
  • Year and Date: 2015-08-23
  • Int'l Joint Research