Human Brain-Dead Recipient Model in Solid Organ Xenotransplantation: A Scoping Review of Technical and Ethical Issues

Solid organ xenotransplantation using gene-edited porcine organs has emerged as a potential approach to address the global organ shortage. As preclinical animal models have demonstrated prolonged graft survival, research efforts have increasingly shifted toward clinical translation. In this context, the brain-dead recipient model has been explored as a complementary translational platform, while also raising important scientific, ethical, and regulatory questions.

This scoping review followed the Arksey and O'Malley framework, with literature searches conducted on the Web of Science Core Collection, Scopus, and PubMed. Experimental studies involving the brain-dead recipient model in solid organ xenotransplantation, as well as commentary or perspective articles addressing related technical and ethical issues were included and synthesized.

Twenty-six publications were included, comprising 11 experimental studies and 15 commentary articles. The experimental studies reported 13 solid organ xenotransplantation cases in brain-dead recipients from the United States and China, involving kidney, heart, liver, and lung transplantation. Most studies showed good immediate graft function without hyperacute rejection. Commentary articles presented diverse perspectives, noting both translational potential and limitations related to study design, short observation periods, and ethical oversight, including informed consent.

The brain-dead recipient model occupies a limited but distinct position in xenotransplantation research, offering short-term translational insights while posing persistent ethical and regulatory challenges. Clarifying its context-dependent role, together with improved ethical oversight and regulatory guidance, will be essential for its responsible use and for sustaining public trust as the field moves toward clinical application.