A novel preclinical model of cDCD lung transplantation with implications for necroptosis
Abstract
This study established a novel rat model that simulates controlled donation after circulatory death (cDCD) lung transplantation (LTx), and investigated necroptosis as a therapeutic target to improve graft quality using a three-phase experimental design. First, we established a model that reproduced the agonal phase in the donor (Phase I). Second, prolonged warm ischemic time progressively worsened graft function, as evidenced by reduced oxygenation, increased pulmonary edema, and increased necroptosis-related signals in pretransplant samples (Phase II). Accordingly, necrostatin-1 (Nec-1), an inhibitor of receptor-interacting protein kinase 1 (RIPK1), was administered during the pre-mortem, graft-flushing, and peri-transplant periods, which improved graft quality, reduced neutrophil infiltration after reperfusion, and decreased the ratio of phosphorylated mixed lineage kinase domain-like protein to total MLKL (pMLKL/MLKL) in pre-transplant samples, consistent with the attenuation of necroptosis-related signaling. These findings suggested that necroptosis-related signaling during the ischemic phase is associated with graft injury in cDCD LTx, and that RIPK1 inhibition may represent a potential therapeutic strategy for attenuating graft injury under prolonged warm ischemia.
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BibTeX
@article{sakurai2026novel,
title = {{A novel preclinical model of cDCD lung transplantation with implications for necroptosis}},
author = {Teiko Sakurai and Takashi Kanou and Takahiro Matsui and Hideki Nagata and Kenji Kimura and Eriko Fukui and Toru Kimura and Naoko Ose and Yasushi Shintani},
journal = {Scientific Reports},
year = {2026},
month = oct,
doi = {10.1038/s41598-026-76492-y},
url = {https://www.nature.com/articles/s41598-026-76492-y},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - A novel preclinical model of cDCD lung transplantation with implications for necroptosis
AU - Teiko Sakurai
AU - Takashi Kanou
AU - Takahiro Matsui
AU - Hideki Nagata
AU - Kenji Kimura
AU - Eriko Fukui
AU - Toru Kimura
AU - Naoko Ose
AU - Yasushi Shintani
PY - 2026
DA - 2026/10/23
JO - Scientific Reports
DO - 10.1038/s41598-026-76492-y
UR - https://www.nature.com/articles/s41598-026-76492-y
AB - This study established a novel rat model that simulates controlled donation after circulatory death (cDCD) lung transplantation (LTx), and investigated necroptosis as a therapeutic target to improve graft quality using a three-phase experimental design. First, we established a model that reproduced the agonal phase in the donor (Phase I). Second, prolonged warm ischemic time progressively worsened graft function, as evidenced by reduced oxygenation, increased pulmonary edema, and increased necroptosis-related signals in pretransplant samples (Phase II). Accordingly, necrostatin-1 (Nec-1), an inhibitor of receptor-interacting protein kinase 1 (RIPK1), was administered during the pre-mortem, graft-flushing, and peri-transplant periods, which improved graft quality, reduced neutrophil infiltration after reperfusion, and decreased the ratio of phosphorylated mixed lineage kinase domain-like protein to total MLKL (pMLKL/MLKL) in pre-transplant samples, consistent with the attenuation of necroptosis-related signaling. These findings suggested that necroptosis-related signaling during the ischemic phase is associated with graft injury in cDCD LTx, and that RIPK1 inhibition may represent a potential therapeutic strategy for attenuating graft injury under prolonged warm ischemia.
SN - 2045-2322
ER -