Recent landmark clinical translation of xenotransplantation depended upon multiple innovations by the xenotransplant community, including the introduction of a variety of source pig genetic modifications, technical innovations, and novel immunosuppressive strategies, as well as the development of ethical and regulatory frameworks to support translation to the clinic. Each organ, tissue, or cell type intended for xenotransplantation will require application-specific preclinical milestones to be met in order to predict "success", as measured by ethical, safe, and efficacious translation to the clinic. Based on successful pre-clinical results and emerging evidence from decedent studies and initial clinical cases, evidence-based infectious disease, ethical, and regulatory considerations are emerging, and will be the foundations for the application-specific position papers that are currently under development. Here, we describe significant landmark events focusing upon safe and efficacious results underpinned by appropriate guidance documents developed over the past three decades that enabled recent translation to the clinic for heart and kidney xenografts. These steps have been undertaken over the past three decades by the xenotransplant community specifically led by the International Xenotransplantation Association (IXA) in consultation with the Transplantation Society (TTS) and the World Health Organization (WHO) to usher xenotransplantation to the clinic.
Keywords: genetic engineering; guidance; legislation; organ donation; regulations; transgenes; xenotransplantation; xenozoonoses.
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