Development of drug eluting bio-covered stent

• Project/Area Number: 16K19842
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Radiation science
• Research Institution: Nara Medical University
• Principal Investigator: SHIGEO ICHIHASHI 奈良県立医科大学, 医学部, 学内講師 (60597102)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 内皮細胞 / ステント / ステント血栓症 / バイオステント / 血管内治療 / intimal hyperplasia / PAD / Endovascular treatment / SFA / Endothelial layer / 薬剤溶出ステント / 内膜過形成 / カバードステント / 平滑筋細胞 / 薬剤溶出型ステント

Outline of Final Research Achievements

We have developed a drug-eluting bio-covered stent to prevent stent thrombosis, which can be a problem after drug-eluting stent placement. A part of femoral vein of two Beagle dogs was collected and endothelial cells were separately cultured. The stent used was Zilver PTX (COOK Japan, 6 mm diameter). Fibrin gel was injected around the stent to provide a substrate for endothelial cell attachment. A solution containing 4 × 10 6 endothelial cells per ml was injected into the stent to attach the endothelial cells. The stents were implanted in the jugular vein of the beagles. One month after angiography, both stents placed in the jugular vein were occluded due to thrombosis.

Academic Significance and Societal Importance of the Research Achievements

高齢化社会が到来し、低侵襲治療である血管内治療が広く普及している。ステント治療成績を改善するために薬剤溶出ステントが開発されたが、溶出する薬剤によって内皮細胞によるステントの被覆が妨げられ、ステント血栓症を惹起するリスクがある。内皮細胞を予め生着させた薬剤溶出ステントを開発することで、ステント血栓症の発生を抑制し、長期成績を改善させる目的で本研究が実施されたが、結果的には1ヶ月での血栓閉塞が認められた。内皮細胞生着の素地に用いたフィブリン膜の構造上の問題が大きいと考えているが、今後は違う素材の使用の検討含め、改良の余地がある。

Research Products

• [Journal Article] Bio-Based Covered Stents: The Potential of Biologically Derived Membranes. (2019)
  • Author(s): Ichihashi S, Fernandez-Colino A, Wolf F, Rojas-Gonzalez DM, Kichikawa K, Jockenhoevel S, Schmitz-Rode T, Mela P.
  • Journal Title: Tissue Eng Part B Rev. Volume: 25 Issue: 2 Pages: 135-151
  • DOI: 10.1089/ten.teb.2018.0207
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] In Vitro Quantification of Luminal Denudation After Crimping and Balloon Dilatation of Endothelialized Covered Stents. (2017)
  • Author(s): Ichihashi S, Wolf F, Schmitz-Rode T, Kichikawa K, Jockenhoevel S, Mela P.
  • Journal Title: Cardiovasc Intervent Radiol. Volume: 40 Pages: 1229-1236
  • Peer Reviewed