Organ transplants of the future: planning for innovations including xenotransplantation

Abstract

The future clinical application of animal-to-human transplantation (xenotransplantation) is of importance to society as a whole. Favourable preclinical data relevant to cell, tissue and solid organ xenotransplants have been obtained from many animal models utilizing genetic engineering and protocols of pathogen-free husbandry. Findings have reached a tipping point, and xenotransplantation of solid organs is approaching clinical evaluation, the process of which now requires close deliberation. Such discussions include considering when there is sufficient evidence from preclinical animal studies to start first-in-human xenotransplantation trials. The present article is based on evidence and opinions formulated by members of the European Society for Organ Transplantation who are involved in the Transplantation Learning Journey project. The article includes a brief overview of preclinical concepts and biology of solid organ xenotransplantation, discusses the selection of candidates for first-in-human studies and considers requirements for study design and conduct. In addition, the paper emphasizes the need for a regulatory framework for xenotransplantation of solid organs and the essential requirement for input from public and patient stakeholders.

Current Aspects of Xenotransplantation in Human

“…In xenotransplantation, there is a risk of transmitting infectious agents from animal to the human recipient [47]. The porcine endogenous retrovirus or PERV is a permanent part of the genome in all mammals which means that not only all recipients will be exposed to the virus, but the risk of transferring the virus to the recipient also cannot be minimized by just selecting the animal from strictly controlled herds [24,37,48].…”

“…Nowadays, a number of countries such as the USA and the UK already have guidelines for clinical trials with xenotransplantation, while some countries are still far behind [3,48,49]. This also raises concern that countries might take advantage of attracting desperate patients who need transplantation by creating xenotransplantation programs [7,30,47].…”

Xenotransplantion: Defeating the “Shumway Curse” An Interview With Drs. Bartley Griffith, Jayme Locke, Robert Montgomery, and Bruno Reichart

“…On Sep. 30, 2021, Dr. Locke transplanted two genetically modified pig kidneys inside the abdomen of a brain-dead human after removing the recipient's native kidneys. Urine production for over 72 hours was also observed ( 1 ).…”

“…The key to these successes seems to have been the availability of pigs genetically engineered to evade xenogeneic rejection mechanisms ( 1 ) .…”

Special Issue “New Therapies of Liver Diseases”

“…New and old pharmacological therapies have been applied in a better way based on the new insights obtained in the pathophysiological studies. Moreover, the increased application of technology innovations, both in diagnostic imaging [ 2 ] and in surgery [ 3 ], enable the cure rate to be increased in patients with advanced liver diseases.…”