Development of bioartificial pancreatic islets using a novel device and coating method

• Project/Area Number: 17H04276
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General surgery
• Research Institution: National Center for Global Health and Medicine
• Principal Investigator: Shimoda Masayuki 国立研究開発法人国立国際医療研究センター, その他部局等, 膵島移植プロジェクト長 (40640529)
• Co-Investigator(Kenkyū-buntansha): 寺村 裕治 東京大学, 大学院工学系研究科(工学部), 准教授 (10365421)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000); Fiscal Year 2019: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2018: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2017: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
• Keywords: バイオ人工膵島 / 1型糖尿病 / 膵島移植 / ランゲルハンス島 / 移植・再生医療 / 異種移植 / バイオマテリアル / PEG脂質

Outline of Final Research Achievements

An ultra-thin coating islet structure was achieved by coating the surface of the islet with biocompatible polyethylene glycol-bound lipids (PEG lipids) and branched PEG derivatives. The optimal conditions for the PEG lipid and the branched PEG derivative were investigated and found. Encapsulated porcine pancreatic islets were transplanted into diabetic mice to evaluate the function and safety of the graft. There were no serious adverse events attributable to the graft until 3 months after transplantation, and individuals with normalized blood glucose levels for 3 months.

Academic Significance and Societal Importance of the Research Achievements

本研究のアプローチは多くの１型糖尿病患者、さらに日本人に多いインスリンが不足するタイプの2型糖尿病患者の根治治療につながる。ドナー不足の問題が解消され、免疫抑制剤が不要になれば安全性が高いのみならず医療コストも低く、社会に与えるインパクトが大きい。さらに本研究のコーティング・カプセル技術はiPS細胞由来膵島などの再生医療にも応用可能である。一方、本研究は異種移植・再生医療の実用化を目指すものであり、最先端のフロンティア領域である。

Research Products

• [Journal Article] Pig Islet Transplant (2019)
  • Author(s): Shimoda Masayuki
  • Journal Title: Xenotransplantation - Comprehensive Study Volume: Edited Volume
  • DOI: 10.5772/intechopen.88324
  • ISBN: 9781789856637, 9781789856644
  • Peer Reviewed
• [Journal Article] Optimization of Islet Microencapsulation with Thin Polymer Membranes for Long-Term Stability (2019)
  • Author(s): Shota Toda, Kenta Asawa, Artin Fattah, Naoko Nakamura, Kristina N Ekdah, Bo Nilsson, Yuji Teramura
  • Journal Title: Micromachines Volume: 10 Issue: 11 Pages: 755-755
  • DOI: 10.3390/mi10110755
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A human whole-blood model to study the activation of innate immunity system triggered by nanoparticles as a demonstrator for toxicity (2019)
  • Author(s): Kristina N Ekdahl, Karin Fromell, Camilla Mohlin, Yuji Teramura, and Bo Nilssona
  • Journal Title: Sci Technol Adv Mater Volume: 20(1) Issue: 1 Pages: 688-698
  • DOI: 10.1080/14686996.2019.1625721
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Modification of human MSC surface with oligopeptide-PEG-lipids for selective binding to activated endothelium (2019)
  • Author(s): Makoto Noiri, Kenta Asawa, Naoya Okada1, Tomonobu Kodama, Yuichi Murayama, Yuuki Inoue, Kazuhiko Ishihara, Kristina N Ekdahl, Bo Nilsson, and Yuji Teramura
  • Journal Title: J Biomed Mater Res Part A Volume: - Issue: 8 Pages: 1779-1792
  • DOI: 10.1002/jbm.a.36697
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Islet xenotransplantation for the treatment of type 1 diabetes. (2018)
  • Author(s): Shimoda M, Matsumoto S
  • Journal Title: OBM Transplantation Volume: 2(2) Issue: 2 Pages: 008-008
  • DOI: 10.21926/obm.transplant.1802008
  • Peer Reviewed
• [Journal Article] Thioacetamide-induced hepatic fibrosis in the common marmoset (2018)
  • Author(s): Inoue T, Ishizaka Y, Sasaki E, Lu J, Mineshige T, Yanase M, Sasaki E, Shimoda M
  • Journal Title: Experimental Animals Volume: 67 Issue: 3 Pages: 321-327
  • DOI: 10.1538/expanim.17-0156
  • NAID: 130007421956
  • ISSN: 0007-5124, 1341-1357, 1881-7122
  • Peer Reviewed