酵素技術が初のヒト試験を突破、普遍的臓器移植に道(UBC enzyme technology clears first human test toward universal donor organs for transplantation)

ad

2025-10-03 カナダ・ブリティッシュコロンビア大学 (UBC)

ブリティッシュコロンビア大学(UBC)の研究チームは、血液型Aの腎臓を酵素処理によってO型へ変換し、初のヒト移植実験に成功した。脳死ドナーの腎臓を変換し、2日間拒絶反応なく機能したことを確認。従来の免疫抑制法と異なり、臓器側の抗原を除去する手法で、血液型不適合移植の壁を克服できる可能性がある。UBCが2019年に発見した2種の高活性酵素が、血管表面の糖鎖を切断して抗原を除去する原理を応用。今後は臨床試験を目指し、スピンオフ企業Avivo Biomedicalが開発を進める。成果はNature Biomedical Engineering誌に掲載。

酵素技術が初のヒト試験を突破、普遍的臓器移植に道(UBC enzyme technology clears first human test toward universal donor organs for transplantation)

The kidney, pre-transplant, in a perfusion device which is used to circulate a solution that contains the converting enzymes. Source: Nature Biomedical Engineering.

<関連情報>

酵素変換O型腎臓は、ヒトの死体モデルにおいて超急性拒絶反応を起こさずにABO不適合移植を可能にする Enzyme-converted O kidneys allow ABO-incompatible transplantation without hyperacute rejection in a human decedent model

Jun Zeng,Ming Ma,Ze Tao,Zhengsheng Rao,Chaomeng Wu,Saifu Yin,Xiaojuan Jiang,Guo Chen,Zhiling Wang,Dan Huang,Mengli Zhu,Ling Liu,Wenqian Huo,Hao Yang,Hui Guo,Gang Chen,Feng Li,Chengyu Zheng,Dajiu Huang,Peter Rahfeld,Jayachandran N. Kizhakkedathu,Stephen G. Withers,Xiaofeng Lu,Keqin Zhang,… Turun Song
Nature Biomedical Engineering  Published:03 October 2025
DOI:https://doi.org/10.1038/s41551-025-01513-6

Abstract

ABO-incompatible kidney transplantation is widely used to meet the escalating need for organs. Current recipient-centric desensitization protocols involving antibody depletion through plasmapheresis increase the risk of infections, perioperative bleeding events and costs. Here we present a donor-centric desensitization protocol, converting type-A kidneys into enzyme-converted O kidneys during hypothermic perfusion to remove the A antigen from the kidneys. An ex vivo model resulted in no antibody-mediated injury. Encouraged by this, an enzyme-converted O kidney was transplanted into a type-O brain-dead recipient with a high titre of anti-A antibody, and no hyperacute rejection was observed. The graft was well tolerated with no evidence of antibody-mediated rejection for 2 days. Antibody-mediated lesions and complement deposition were found starting 3 days post-transplant, coinciding with A-antigen regeneration, and later higher Banff scores, suggesting an immune-mediated response. Single-cell sequencing confirms the elevated expression of accommodation-related genes, suggesting the potential for longer-term tolerance. This study provides a donor-centric organ engineering strategy and has the potential to broaden the reach of ABO-incompatible kidney transplantation, improving the fairness of and access to organ allocation.

医療・健康
ad
ad
Follow
ad
タイトルとURLをコピーしました