Establish a treatment strategy to diabetic nephropathy using combined kidney and islets transplantation

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H05403
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General surgery
• Research Institution: Kagoshima University
• Principal Investigator: YAMADA Kazuhiko 鹿児島大学, 総合科学域総合研究学系, 教授 (40241103)
• Co-Investigator(Kenkyū-buntansha): 佐原 寿史 鹿児島大学, 総合科学域総合研究学系, 准教授 (90452333) ; 清水 章 日本医科大学, 大学院医学研究科, 大学院教授 (00256942)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 移植・再生医療 / 免疫寛容 / 膵島移植 / 大動物 / 腎臓移植 / 骨髄移植 / サル / キメラ

Outline of Final Research Achievements

This project aimed to cure diabetic nephropathy by utilizing a composite islet-kidney combined with hematopoietic cell transplantation. Over a three-year period, the goal of a three-step progressive improvement in the immune tolerance-inducing immunosuppressive therapy was achieved. Although we have exceeded 200 days survival of composite islet-kidney grafts with first-generation immunosuppression, further efforts are required to reduce drug-induced islet toxicity and improve donor chimerism. The second step demonstrated evidence of BM engraftment at day 37 and rejection free islet-kidney grafts, and the third step further improved % and duration of donor chimerism. With the establishment of the leukapheresis procedure, we have achieved peripheral chimerism for more than 30% over 6 weeks following transplantation, as well as further bone marrow chimerism.

Free Research Field

外科学一般

Academic Significance and Societal Importance of the Research Achievements

独自の血管再構築による膵島腎（Islet-Kidney: IK）移植を軸とした、臨床応用可能な糖尿病性腎症患者に対する根治的戦略の確立をはかる本申請研究は、国際的学術誌に認められた自らの成果に基づく計画のもとに遂行され、糖尿病性腎症の根治的治療としての革新的免疫寛容誘導戦略の確立と臨床応用性が、大きく前進するものと確信する。本戦略の臨床応用によって、終末期糖尿病性腎症患者のQOL向上のみならず、医療費削減という社会的観点からも大きな貢献を果たす。