Xenotransplantation: A New Era

Abstract

Organ allotransplantation has now reached an impassable ceiling inherent to the limited supply of human donor organs. In the United States, there are currently over 100,000 individuals on the national transplant waiting list awaiting a kidney, heart, and/or liver transplant. This is in contrast with only a fraction of them receiving a living or deceased donor allograft. Given the morbidity, mortality, costs, or absence of supportive treatments, xenotransplant has the potential to address the critical shortage in organ grafts. Last decade research efforts focused on creation of donor organs from pigs with various genes edited out using CRISPR technologies and utilizing non-human primates for trial. Three groups in the United States have recently moved forward with trials in human subjects and obtained initial successful results with pig-to-human heart and kidney xenotransplantation. This review serves as a brief discussion of the recent progress in xenotransplantation research, particularly as it concerns utilization of porcine heart, renal, and liver xenografts in clinical practice.

Current state of clinical trials on xenograft

“…Similarly, publications related to these trials are very low (only three publications). This could be explained by the fact that xenotransplantation is a new field of science, and application on human subject is recently moving forward 43 . This also explains why most trials had short duration of time, since long‐term clinical studies complements the results of short‐term 44 .…”

Comparative analysis of ECG records depending on body position in domestic swine (Sus scrofa domestica)

“…Due to the increasing popularity of pigs as companion animals, providing veterinary aid in this species will require getting increasingly more knowledge of this species as a potential patient in veterinary clinics [ 1 , 2 ]. Also, recent spectacular achievements in the field of xenotransplantology and model research concerning, inter alia, heart and kidney transplants show how important it is to broaden knowledge about this species [ 9 – 12 ]. Increasingly advanced medical procedures are performed in swine, including orthopedic surgeries or minimally invasive cardiology procedures, both in companion pigs and during model tests [ 23 , 24 , 32 ].…”

“…The pig is also a leading species under investigation for xenotransplantation between animals and humans [ 9 – 11 ]. Recent studies report on successful kidney and heart xenografts [ 12 ]. The swine is an animal well discovered not only as a laboratory animal but also as a farm animal, thanks to which a wide knowledge of its needs, specific maintenance, and welfare is available [ 13 , 14 ].…”

In defense of xenotransplantation research: Because of, not in spite of, animal welfare concerns

“…This by itself does not settle the issue, because xenotransplantation could cause infectious diseases that harm persons, but that is an additional reason why research involving animals is needed so that we might be able to avoid these costs. 4 Pressing the "research on animals" button offers a good chance at securing a better future for people in organ failure.…”

“…There is reason to be optimistic that this future is not far off, evidenced by the registration for a phase I clinical trial to begin with 20 patients with end‐stage kidney disease 1 . Within the last year, researchers attached genetically‐altered porcine kidneys and hearts to “brain‐dead” bodies, 2,3 and a transgenic pig heart was transplanted into a living but severely ill patient in a procedure that was granted emergency authorization 4,5 . In each case, no hyperacute rejection of the organ was reported before the studies were terminated.…”