Ex-vivo pretreatment of islets with Mitomycin-C have a potential to induce specific immune response for peripheral tolerance

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K16512
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General surgery
• Research Institution: Fukushima Medical University
• Principal Investigator: Sato Naoya 福島県立医科大学, 医学部, 助教 (90622332)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: 膵島移植 / 免疫寛容 / preconditioning / Mitomycin-C

Outline of Final Research Achievements

Introduction: Our previous study demonstrated that ex-vivo Mitomycin-C(MMC) pretreatment of islets reduced immunogenicity, enhancing graft survival without immunosuppression. The aim of this study is to investigate an immunological mechanism to enhance graft survival of MMC-treated islets. Methold:Isolated islets with MMC pretreatment were implanted to renal subcapsular space of diabetic mice. Immune response to xenograft in over-100-days after grafting was evaluated by histological analysis.Result:Histological and immunohistochemical analyses of the implant site revealed that infiltration of CD3-positive T cell was decreased in MMC-treated islets in early phase after transplantation. In all mice survived over-100-days, CD3-positive T cell aggregation surround by CD45R-positive B cell was found near xenograft. Conclusion: Ex-vivo MMC pretreatment of islets reduced early phase immune response to xenograft and induced characteristic immune response in peripheral transplantation site.

Free Research Field

膵島移植

Academic Significance and Societal Importance of the Research Achievements

移植後免疫抑制剤を加えずに、移植前処置のみでグラフトの長期生着をもたらすプロトコールの確立は、膵島移植のみならず移植医療の究極的な目標である。我々の既報ではMMC処置によるSublethal cell stressは細胞死を回避し、免疫応答の抑制により膵島移植片の生着率の改善をもたらしている。これは移植前処置における理想的な免疫抑制モデルとなる可能性を秘めており、この細胞死の回避と免疫寛容メカニズムを解明する事により、最適な移植前処置の確立と膵島移植成績の向上へつながるものと期待される。