Xenograft

Xenotransplantation (''xenos-'' from the Greek meaning "foreign" or strange), or heterologous transplant, is the transplantation of living cells, tissues or organs from one species to another. Such cells, tissues or organs are called xenografts or xenotransplants. It is contrasted with allotransplantation (from other individual of same species), syngeneic transplantation or isotransplantation (grafts transplanted between two genetically identical individuals of the same species) and autotransplantation (from one part of the body to another in the same person).

Xenotransplantation of human tumor cells into immunocompromised mice is a research technique frequently used in pre-clinical oncology research.

Human xenotransplantation offers a potential treatment for end-stage organ failure, a significant health problem in parts of the industrialized world. It also raises many novel medical, legal and ethical issues. A continuing concern is that many animals, such as pigs, have a shorter lifespan than humans, meaning that their tissues age at a quicker rate. (Pigs have a maximum life span of about 27 years.) Disease transmission (xenozoonosis) and permanent alteration to the genetic code of animals are also causes for concern. Similarly to objections to animal testing, animal rights activists have also objected to xenotransplantation on ethical grounds. A few temporarily successful cases of xenotransplantation are published.

It is common for patients and physicians to use the term "allograft" imprecisely to refer to either allograft (human-to-human) or xenograft (animal-to-human), but it is helpful scientifically (for those searching or reading the scientific literature) to maintain the more precise distinction in usage.

History

The first serious attempts at xenotransplantation (then called heterotransplantation) appeared in the scientific literature in 1905, when slices of rabbit kidney were transplanted into a child with chronic kidney disease. In the first two decades of the 20th century, several subsequent efforts to use organs from lambs, pigs, and primates were published.

Scientific interest in xenotransplantation declined when the immunological basis of the organ rejection process was described. The next waves of studies on the topic came with the discovery of immunosuppressive drugs. Even more studies followed Joseph Murray's first successful renal transplantation in 1954 and scientists, facing the ethical questions of organ donation for the first time, accelerated their effort in looking for alternatives to human organs.

Non-human kidney to a human

In 1963, doctors at Tulane University attempted chimpanzee-to-human renal transplantations in six people who were near death; after this and several subsequent unsuccessful attempts to use primates as organ donors and the development of a working cadaver organ procuring program, interest in xenotransplantation for kidney failure dissipated. Out of 13 such transplants performed by Keith Reemtsma, one kidney recipient lived for nine months, returning to work as a schoolteacher. At autopsy, the chimpanzee kidneys appeared normal and showed no signs of acute or chronic rejection.

Non-human heart to a human

An American infant girl known as "Baby Fae" with hypoplastic left heart syndrome was the first infant recipient of a xenotransplantation, when she received a baboon heart in 1984. The procedure was performed by Leonard Lee Bailey at Loma Linda University Medical Center in Loma Linda, California. Fae died 21 days later due to a humoral-based graft rejection thought to be caused mainly by an ABO blood type mismatch, considered unavoidable due to the rarity of type O baboons. The graft was meant to be temporary, but unfortunately a suitable allograft replacement could not be found in time. While the procedure itself did not advance the progress on xenotransplantation, it did shed a light on the insufficient amount of organs for infants. The story made such an impact that the crisis of infant organ shortage improved for that time.

Non-human heart, lungs, and kidneys to a human

The first transplant of a non-genetically modified pig's heart, lungs and kidneys into a human was performed in Sonapur, Assam in India in mid-December 1996, and was announced in January 1997. The recipient was Purno Saikia, a 32-year-old terminally-ill man; he died shortly after the operation of multiple infections. The Indian cardiothoracic surgeon Dhani Ram Baruah and two of his associates, Jonathan Ho Kei-shing (of the Hong Kong-based Prince of Wales Medical Institute) and C.S. James, performed the surgeries. Baruah claimed that Saikia had failed to respond to conventional surgery, and that the patient and his family had consented to the procedure.

All three involved in the surgery were arrested on January 9, 1997, for the alleged violation of the Transplantation of Human Organs and Tissues Act of 1994. Baruah was dismissed in medical circles as a "mad scientist" and the procedure was dubbed a "hoax". Baruah himself signed a statement saying he had done no transplant, but then alleged that the confession was forced from him. They were found guilty of unethical procedure and culpable homicide and imprisoned for 40 days. Dhani Ram Baruah's surgical institute was also found to be without necessary registration.

Critics said Dhani Bam Baruah's claims and medical procedures were neither taken seriously nor accepted by the scientific community because he never got his findings scientifically peer-reviewed. Past complaints of ethics violations during surgeries in Hong Kong by Baruah and Ho had occurred in 1992, when they had implanted heart valves, developed by Baruah, made of animal tissue. A year later, six patients died. The Asian Medical News reported that "grave concerns" were expressed "over the procedure and ethics of the implementation".

Genetically engineered non-human kidney to a human

In September 2021, surgeons led by Robert Montgomery performed the first genetically engineered pig kidney xenotransplant to a brain-dead human at NYU Langone Health with no sign of immediate rejection (partly because the pig thymus gland was transplanted as well). The kidney was procured from a pig with only a single gene modification: the removal of alpha-gal