The case for xenotransplantation

Abstract

The availability of organs and cells from deceased humans for transplantation is not meeting the demand. Xenotransplantation, specifically the transplantation of organs and cells from genetically-engineered pigs, could resolve this problem. Diabetic monkeys have remained normoglycemic and insulin-independent after pig islet transplantation for >1 year, and a pig heterotopic (non-life-supporting) heart transplant recently reached the one-year milestone in a baboon. With these encouraging results, why is it that, with some notable exceptions, research into xenotransplantation has received relatively little support by industry, government funding agencies, and medical charitable foundations? Industry appears reluctant to support research that will take more than 2–3 years to come to clinical trial, and the funding agencies appear to have been “distracted” by the current appeal of stem cell technology and regenerative medicine. It has only been the willingness of living donors to provide organs that has significantly increased the number of transplants being performed worldwide. These altruistic donations are not without risk of morbidity and even mortality to the donor. Although with the best of intentions, we are therefore traversing the Hippocratic Oath of doctors to “do no harm”. This should be a stimulus to fund exploration of alternative approaches, including xenotransplantation.

Recent advances in understanding xenotransplantation: implications for the clinic

“…If the immune barriers to clinical pig organ transplantation can be completely overcome, the impact that xenotransplantation will have on clinical medicine will be immense [3-5]. There are a number of advantages of pig organ transplantation over allotransplantation (Table 2).…”

“…As with many other fields of medical research, the major factor inhibiting progress is lack of sufficient funding from governmental agencies, medical charitable foundations, and industry (discussed in [5]). Perhaps, as the field progresses towards clinical trials of solid organs, pharmaceutical and biotechnology companies will begin to take a serious interest again.…”

“…Xenotransplantation, i.e., cross-species transplantation, e.g., between pig and human, offers the prospect of unlimited organs and cells for clinical transplantation [3-5]. The history of this experimental field has been reviewed elsewhere and will not be reviewed again except to state that kidney transplants from nonhuman primates (NHPs) into humans in the 1960s demonstrated that the immune response was greater than to an allograft [6,7].…”

Renal xenotransplantation: experimental progress and clinical prospects

“…4 Kidney xenotransplantation has a long history going back >100 years, 5 mainly relating to the clinical transplantation of kidneys from nonhuman primates (NHPs). It is only relatively recently that significant progress has been made in the transplantation of pig kidneys in the experimental laboratory.…”

The White House Organ Summit

“…The entire problem of donor organ availability might be resolved by the use of genetically engineered pig organs within the next few years (10), and yet it appears its potential has been ignored. Yet, with regard to the potential to provide organs for clinical transplantation, the field of xenotransplantation research is far advanced compared with those of stem cell or regeneration technology and other approaches directed towards this aim.…”