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Xenotransplantation

[zen-uh-trans-plant, ‐plahnt, zee-nuh‐]

Xenotransplantation (xeno- from the Greek meaning "foreign") is the transplantation of living cells, tissues or organs from one species to another such as from pigs to humans (see Medical grafting). Such cells, tissues or organs are called xenografts or xenotransplants. The term allotransplantation refers to a same-species transplant. 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 pigs have different lifespans than humans and their tissues age at a different rate. Disease transmission (xenozoonosis) and permanent alteration to the genetic code of animals are also a cause for concern.

Because there is a worldwide shortage of organs for clinical implantation, about 60% of patients awaiting replacement organs die on the waiting list. Recent advances in understanding the mechanisms of transplant organ rejection have brought science to a stage where it is reasonable to consider that organs from other species, probably pigs, may soon be engineered to minimize the risk of serious rejection and used as an alternative to human tissues, possibly ending organ shortages.

Other procedures, some of which are being carefully investigated in early clinical trials, aim to use cells or tissues from other species to treat life-threatening and debilitating illnesses such as cancer, diabetes, liver failure and Parkinson's disease. If vitrification can be perfected it could allow for long-term storage of xenogenic cells, tissues and organs so they would be more readily available for transplant.

There are only a few published successful xenotransplant procedures. Some patients who were in need of liver transplants were able to use pig livers that were on a trolley by their bedside successfully until a proper donor liver was available.

Problems

Immune rejection remains the biggest challenge for xenotransplantation. The problem exists even for human to human transplants (known as allotransplantation), but is more serious for transplants between different species. Nearly all mammalian cells have markers which enable the immune system to recognise them as being foreign. The more different the genetic code between the donor organ and recipient, the greater the difference between a "self" marker and a "foreign" marker. Some companies are currently developing transgenic animals such as pigs, that produce human markers to try and lessen the chance of rejection.

Cross-species transplants are more likely to produce host-vs-graft or graft-vs-host reactions than same-species transplants, because of the lack of antigenic similarity. Organisms which have been genetically engineered to reduce this difference have been produced but are not yet used to any significant degree in medical care.

A worrisome element of xenotransplantation is the potential for infectious disease to spread from the donor animal, which is called xenozoonosis. One example is porcine endogenous retroviruses (PERVs) which are viruses within pigs that pigs are immune to, but can infect isolated human cells in cell culture. Some recipients of pig neural cell transplants have had to agree to never donate blood, take frequent blood tests and use safe sex methods for the rest of their lives due to the risk of spreading such viruses. However, the patients who have received these pig cell transplants have yet to show any PERV-type infection. The situation with other animals is currently unknown.

Acceptance

Xenografts have been a controversial procedure since they were first attempted. Many, including animal rights groups, strongly oppose killing animals in order to harvest their organs for human use. Legitimate medical concerns exist about possible disease transfer between animals and humans, such as the porcine endogenous retrovirus found in pig tissues. Religious beliefs, such as the Jewish and Muslim prohibition against eating pork, have been sometimes thought to be a problem, however according to a Council of Europe documentation both religions agree that this rule is overridden by the preservation of human life.

In general, however, the use of pig and cow tissue in humans has been met with little resistance. The tissue is harvested from agricultural animals that were already being butchered, which is less offensive to most people than the idea of raising a primate (which due to its genetic similarity would produce more suitable organs for transplants to humans) solely as an organ donor. Similarly, while some individual Jews may not wish to receive a pig valve based on their personal beliefs, the rabbinical view is that the use of pig valves in humans is not a violation of kashruth law. In fact, killing a pig in order to save a human life is a requirement in the Jewish faith, under the laws of pikuach nefesh.

In 2005, the Australian National Health and Medical Research Council declared a five-year moratorium on all animal-to-human transplantation, concluding that the risks of transmission of animal viruses to patients and the wider community have not yet been resolved .