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While only case reports have been published to date, the first clinical trials for kidney xenotransplantation are now ongoing. This transition to clinical practice presents multiple implementation challenges for establishing scalable transplant programs while ensuring patient safety. Machine perfusion is expected to play a critical role in addressing these challenges by serving as a central platform for organ preservation, assessment, transport, and therapeutic intervention. Given the limited number of designated pathogen\u2010free (DPF) breeding facilities, regional and international organ transport depends on robust preservation strategies during transit. Additionally, perfusion devices enable essential pre\u2010transplant screening for zoonotic pathogens, a crucial safety measure unique to xenotransplantation. Further, given recent developments that allow for multi\u2010day perfusion of grafts, wild\u2010type grafts could potentially be genetically modified while being perfused\n                    <jats:italic>ex situ<\/jats:italic>\n                    . Beyond these perfusion modalities of isolated whole organs, machine perfusion offers a new therapeutic approach for patients with acute liver failure. Here, cross\u2010circulation between a perfused genetically modified porcine organ and the patient can provide temporary liver replacement therapy. This mini\u2010review summarizes the transformative potential of machine perfusion technology in clinical xenotransplantation with a focus on livers.\n                  <\/jats:p>","DOI":"10.1111\/xen.70131","type":"journal-article","created":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T02:17:57Z","timestamp":1777774677000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Xenoperfusion\u2014The Transformative Role of Machine Perfusion in Xenotransplantation"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9501-4952","authenticated-orcid":false,"given":"Florian","family":"Huwyler","sequence":"first","affiliation":[{"name":"Macromolecular Engineering Laboratory ETH Zurich  Zurich Switzerland"},{"name":"Hub For Translational Research and Liver\/GI Health University of Zurich, ETH Zurich, University of Fribourg  Zurich 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