Mechanism and regulation of the complement activity in kidney xenotransplantation

Hirose, Takayuki; Hotta, Kiyohiko; Otsuka, Ryo; Seino, Ken-Ichiro

Mechanism and regulation of the complement activity in kidney xenotransplantation

Hirose, Takayuki; Hotta, Kiyohiko; Otsuka, Ryo et al.

Transplantation Reviews, 2025, 39(3), 100931

Permalink : https://hdl.handle.net/2115/97756

このアイテムのアクセス数:53件（2026-07-14 19:25 集計）

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アクセス権	open access
URI	https://hdl.handle.net/2115/97756
タイトル	Mechanism and regulation of the complement activity in kidney xenotransplantation
著者	Hirose, Takayuki ; Hotta, Kiyohiko ; Otsuka, Ryo ; Seino, Ken-Ichiro
e-Rad_Researcher 80963595 著者名 Hirose, Takayuki
e-Rad_Researcher 90443936 著者名 Hotta, Kiyohiko
著者名 Otsuka, Ryo
e-Rad_Researcher 20312845 著者名 Seino, Ken-Ichiro
言語	英語
キーワード	Complement
	Innate immunity
	Kidney transplantation
	Xenotransplantation
発行日	2025-04-13
出版者	Elsevier
収録物名	Transplantation Reviews
巻(号)	39(3)
ページ	100931
抄録	Xenotransplantation is emerging as one of several potential solutions for addressing organ donor shortages, with significant progress bringing it closer to clinical application. However, challenges remain, particularly concerning complement system dysregulation caused by species differences, as well as xenoantigens and coagulopathy. Complement regulatory proteins expressed on endothelial cells of donor xenografts are less compatible with complement components in recipients. These difficulties contribute to hyperacute rejection, characterized by antibody-mediated complement activation that destroys the graft within 24 h. Moreover, because molecules are incompatible across different species, ischemia-reperfusion injury or infection can easily elicit complement activity via all three pathways, resulting in xenograft loss via complement-mediated vascular injury. Complement activity also stimulate innate and adaptive immune cells. To address this issue, genetic modifications in donor pigs and the development of novel medicines have been tested in preclinical models with promising results. Pigs modified to express human complement-regulating molecules such as CD46, CD55, and CD59 have shown longer kidney xenograft survivals over years in preclinical models with nonhuman primates, paving the way for clinical trials. Anti-complement component agents such as C1 esterase and C5 inhibitors have also been shown to increase xenograft survivals. This review examines the role of the complement system in kidney xenotransplantation, emphasizing new research and clinical trial advancements.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
権利情報	© 2025. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/
PISSN	0955-470X
EISSN	1557-9816
関連情報	PMID 40233672
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1016/j.trre.2025.100931