Life science backgrounder: What is xenotransplantation?

Xenotransplantation is the transplantation of organs or cells from a non-human animal into a human, as the name suggests, with ‘xeno’ coming from the Greek work for ‘foreign.’ Unlike the transplantation of things like heart valves from animals, xenotransplantation involves using living cells or organs.

Applications of xenotransplantation

Xenotransplantation can be used in a number of ways, the first being through direct transplantation, such as a whole organ like a heart or kidney. Given the shortages of organs available for transplantation, xenotransplantation offers a greater resource of potentially life-saving organs for transplant.

Various animals have been considered for organs xenotransplantation, including primates like chimpanzees and baboons, although it’s generally considered that pigs offer the greatest potential as a source of organs given their relative similarity in size to humans.

Xenotransplantation can also involve cellular therapies, where specific animal cells are transplanted or implanted into a human to compensate for deficient functioning. One example being pursued in clinical trials by New Zealand company, Living Cell Technologies, which is implanting insulin-producing cells from pigs into a human with Type 1 diabetes.

The final type of xenotransplantation involves external therapies where cells are grown or filtered outside the body along with animal cells before being transplanted back into the patient.

Pros and cons of xenotransplantation

The primary benefit of xenotransplantation is that the source of the transplanted cells or organs doesn’t have to be human, with all the ethical and practical difficulties entailed. Transplanting organs or cells from farmed pigs, for example, provides a greater availability of potentially life-saving therapies.

However, xenotransplantation isn’t without its challenges, both practical and ethical. On the practical side, one of the greatest issues is overcoming the immunological barrier and having the organ accepted by a human body.

Our immune system has evolved a highly sophisticated system for detecting and eliminating foreign cells, and this system is responsible for rejecting transplanted organs unless appropriate steps are taken to find an organ that is as closely compatible to the host as possible along with immunosuppressive treatments.

One possibility is genetically modifying the xenotransplanted organs to be more compatible with the human immune system so it doesn’t trigger the potentially lethal immune response.

Another challenge with xenotransplantation is managing zoonosis, or the transmission of diseases from animal to human. This is more likely when organs or cells are taken from more closely related animals, such as primates. It is more remote, although still possible, from pigs and other less related mammals.

The virus that is of most concern in animal to human transplantation using pigs as the donor species is the porcine endogenous retrovirus (PERV). PERV is present in most strains of pigs and cannot be removed by raising pigs in sterile conditions. PERV is harmless in pigs, however laboratory research suggests it is possible that PERV could cause disease in humans through animal to human transplantation.

The risk can be minimised by using pigs that do not carry the strain. More than 150 people worldwide who have been transplanted with pig tissue or had their blood pass through pig cells have shown no evidence of infection with a virus or any other infectious agent originating from pigs. Living Cell Technologies operates a pig farm in the south island of New Zealand that uses specially bred pigs in highly controlled environments for just this reason.

Xenotransplantation also faces some ethical issues, although all xenotransplantation trials that are undertaken in Australia have to conform to the strict ethical requirements of any clinical trial, which includes provisions for the treatment of animals.

History of xenotransplantation in Australia

Some clinical trials were conducted by Living Cell Technologies in the early 2000s, but general concerns over zoonosis via any xenotransplantation technology caused both New Zealand and Australia to impose moratoria on xenotransplantation clinical trials.

Many researchers, including Living Cell Technologies’ founder Bob Elliott argued that such a xenotransplantation ban was unwarranted.

However, a New Zealand Ethics Council report in 2005 recommended that xenotransplantation trials could go ahead, and Australia followed suit by lifting is ban on xenotransplantation in 2009.

New trials are now underway exploring Living Cell Technologies’ DIABECELL, a porcine insulin-producing cell product for the treatment of Type 1 diabetes. These trials are taking place in New Zealand and Russia, with plans to run trials in Australia as well.