Xenotransplantation: From research to trial to practice

Animals have been considered potential sources of organs and complex tissues for clinical transplantation, and occasional cross-species transplants have been performed (when human sources were scarce or unavailable) over the past 120 years. However, no clinical xenotransplant has been deemed successful. Today, after extensive efforts to understand the immunological and biological barriers to xenotransplantation and with the application of genetic engineering and other technologies to overcome these barriers, enthusiasm for xenotransplantation has grown again. A small number of clinical xenotransplants have recently been performed, with formal clinical trials either planned or underway. Therefore, it is important to consider whether and how clinical xenotransplantation might move forward. The key to advancing xenotransplantation from research to clinical practice depends on the experience gained-specifically, whether large clinical trials are necessary to prove feasibility and usefulness, or if such proof must be established before initiating large trials. This question prompted the development and publication of a collection of papers in Human Immunology in 2023. With the outcomes of a few clinical xenografts now known, the question is even more relevant. Consequently, an updated commentary and the contents of the collected papers follow.