DOI:10.1097/MOT.0000000000000602 Organ transplantation is the treatment of choice for individuals with end-stage organ disease [1]. It provides good quality of life to individuals with terminal heart, lung, or liver pathologies… Click to show full abstract
DOI:10.1097/MOT.0000000000000602 Organ transplantation is the treatment of choice for individuals with end-stage organ disease [1]. It provides good quality of life to individuals with terminal heart, lung, or liver pathologies [2,3], while significantly prolonging survival in subjects with renal failure compared with dialysis [4–6]. However, transplantation is not available for a large fraction of the patients in need. Due to the limited number of suitable donors and the expanding indications for transplantation, the gap between transplant organ offer and demand is widening. As a result, the yearly mortality rates while on the waiting list are dramatically high, exceeding 10–15% for heart [7,8] and liver transplantation [9]. In the current issue of Current Opinion in Transplantation, Cowan et al. (pp. 5–11) discuss the possibility of using porcine donors as a potential solution to the growing demand for transplantable organs and tissues. In the 1990s, survival of porcine grafts into nonhuman primates (NHPs) did not exceed hours or days due to preexisting antibodies against porcine xenoantigens and inefficient control of innate and adaptive immune responses [5]. However, over the last few years, survival of xenografts in NHP models has been prolonged to almost a year [10,11]. This remarkable result has been obtained by implementing multitargeted strategies includingvarious genetic engineering techniques enabling genome modifications in pigs aiming to reduce the cross-species immunebarrier, effective induction and maintenance immunosuppression, and tolerogenic conditioning [12]. In particular, the CRISPR-associated protein-9 nuclease technology has revolutionized the rapid generation of pigs containing multiple genetic modifications, including knock-outs and knock-ins. These advancements are rapidly transforming xenotransplantation from being the focus of a limited research area into becoming a potentially impactful opportunity for the transplant community to be tested in clinical studies. Amongst the many theoretical advantages of using pigs as a source of graft is the fact that these organs are obtained from young and healthy living animals. Indeed, organs obtained from young living donors have a longer survival than organs obtained
               
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