Development of the tolerance induction method by injecting the cultivated donor cells into anterior chamber of the eye

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10529
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Meiji University of Integrative Medicine
• Principal Investigator: Yamada Jun 明治国際医療大学, 医学教育研究センター, 教授 (80351352)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 角膜移植 / 臓器移植 / 心臓移植 / 角膜内皮細胞 / 免疫寛容

Outline of Final Research Achievements

To establish the tolerance induction method by injecting the cultivated donor cells is the goal of our aim.
Cultivated allogeneic corneal endothelial cell (CEC) injection therapy for CEC dysfunction is now available. To evaluate allogeneic response post CEC injection into the anterior chamber (AC), we developed new experimental models and examined allosensitization and acquisition of transplantation tolerance.Labeled mpCECs in the cryo-injured eyes survived for at least 1 week (N=5). C57BL/6 penetrating keratoplasty allografts at 8-weeks post mpCEC injection never displayed episodes of allogeneic rejection (N=10, 100%, p<0.001). Moreover, more than 50% cardiac allograft survived indefinitely after allogeneic CEC injection. However, other cells including vascular endothelial cells, but not CECs, could not survive anterior chamber of the eye. We need to find the new method for allogeneic tolerance induction.

Free Research Field

移植免疫

Academic Significance and Societal Importance of the Research Achievements

アロ移植は基本的に拒絶される。しかし、前房内に移植を行う角膜内皮細胞移植では拒絶されないだけでなく免疫寛容が誘導される。この生体の特殊な応答を臓器移植に応用できた場合には免疫抑制剤の副作用を軽減でき、安全な移植医療が実現できる。マウスモデルにおいて、角膜内皮細胞移植後に全層角膜移植は100%拒絶されなくなり、心臓移植も無治療で生着できることが判明した。人での実現に向けて、角膜移植を用いずに安全な免疫寛容誘導方法を開発することが今後必要であり、あと一歩新たな知見やアイデアが必要である。