Hypothermic machine perfusion prevents hyperacute graft loss in pig-to-primate kidney xenotransplantation after 5-hours of cold Ischemia

Yu Hisadome; Daniel L Eisenson; WeiLi Chen; Alexander C Schulick; Adam Luo; Michelle R Santillan; Kelly Casella; Du Gu; Mitsuhiro Sekijima; Hisashi Sahara; Daniel Warren; Andrew Cameron; Hayato Iwase; Eugene Shenderov; Kazuhiko Yamada

doi:10.1038/s43856-025-00842-6

Hypothermic machine perfusion prevents hyperacute graft loss in pig-to-primate kidney xenotransplantation after 5-hours of cold Ischemia

Commun Med (Lond). 2025 Apr 15;5(1):117. doi: 10.1038/s43856-025-00842-6.

Authors

Affiliations

¹ Department of Surgery, Division of Transplantation, The Johns Hopkins School of Medicine, Baltimore, MD, USA.
² Department of Oncology, The Johns Hopkins School of Medicine, Baltimore, MD, USA.
³ Division of Experimental Large Animal Research, Life Science and Laboratory Animal Research Unit, Kagoshima University, Kagoshima, Japan.
⁴ Department of Surgery, Division of Transplantation, The Johns Hopkins School of Medicine, Baltimore, MD, USA. kyamada6@jhmi.edu.

Abstract

Background: Xenotransplantation (XTx) is a promising strategy to address the organ shortage. Clinical application will likely require off-site procurement from designated pathogen-free (DPF) facilities, introducing unavoidable cold ischemic time (CIT). The impact of CIT and organ preservation method on graft function in XTx remains unclear.

Methods: We evaluated eight cases of pig-to-baboon kidney xenotransplantation performed after five hours of CIT, comparing static cold storage (SCS) to hypothermic machine perfusion (HMP) preservation. Outcomes were assessed relative to six additional pig-to-baboon transplants performed with minimal CIT.

Results: All grafts preserved with SCS experience hyperacute rejection within 90 min of reperfusion, even in recipients with low levels of preformed anti-pig antibodies. In contrast, all HMP-preserved grafts reperfuse without clinical evidence of injury and maintain function for more than 14 days. Grafts transplanted with minimal CIT show similarly favorable outcomes.

Conclusions: Porcine kidneys are highly sensitive to ischemia-reperfusion injury after cold preservation across xenogeneic barriers. Routine SCS leads to early graft failure, while HMP mitigates ischemic injury and may enable successful clinical XTx despite prolonged CIT.

Plain language summary

Xenotransplantation, or transplanting pig organs into primates or humans, could help solve the shortage of donor organs. However, future transplants will likely involve transporting organs from designated procurement facilities, leading to several hours of organ preservation time during transportation. This study tested how different preservation methods affect pig kidney function after transplant into baboons. Kidneys stored using the standard method (on ice) failed almost immediately, even in recipients with low immune response. In contrast, kidneys preserved with hypothermic machine perfusion—a method that pumps cold fluid through the organ—functioned well for over two weeks. These results suggest that pig kidneys are highly sensitive to cold-related damage and that machine perfusion may be a safer option for preserving organs in future clinical xenotransplantation.

Abstract

Plain language summary

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