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Frequently asked questions (FAQs): Xenotransplantation

On 9 December 2009, the Council of the NHMRC recommended that clinical trials involving animal to human transplantation (xenotransplantation) only be allowed to proceed, when appropriate regulatory and surveillance frameworks have been put in place.

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What is xenotransplantation?

Xenotransplantation is the term used for the transplantation of living cells, tissues or organs from one species to another. NHMRC generally uses the term ‘animal to human transplantation’ to clarify the type of xenotransplantation being discussed (eg from pigs to humans).

There are three types of xenotransplantation; animal external therapies, animal cell therapies and animal organs transplants.

Animal external therapies are procedures that occur outside the body. In this type of therapy, cells or fluids are removed from the patient, cultured (grown) with or filtered through animal cells and then returned to the patient.

Animal cell therapies involve the transplantation of tissues and cells from one species to another. For example; skin, bone or clusters of specialised cells such as pancreatic islet cells (which produce insulin to treat diabetes).

Organ xenotransplants involve the transplantation of whole organs such as hearts and kidneys from one species to another. This is the most complicated type of xenotransplantation because unlike cells and tissues, organs require lots of blood vessels to supply the organ with oxygen and nutrients.

Some animal devices, such as pig heart valves, have been used in humans for many years. These devices are treated so they contain no living cells. Xenotransplants differ from these devices in that they are alive and can perform the same functions as the organ, tissue or cells that they replace.

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Are animal to human transplantation clinical trials permitted in Australia?

Not at present. On 9 December 2009, the Council of the NHMRC recommended that clinical trials involving animal to human transplantation (xenotransplantation) only be allowed to proceed, when appropriate regulatory and surveillance frameworks have been put in place.

As Australia is yet to establish robust regulatory and surveillance frameworks, clinical trials are currently not permitted.

The reasons: NHMRC assessed the risks and benefits of clinical trials with a particular focus on the scientific and technical developments in xenotransplantation research over the last five years. NHMRC concluded that the risks, if appropriately regulated, are acceptable given the potential benefits.

It is important to note NHMRC’s decision relates only to research and does not permit animal to human transplantation to be used as a routine treatment for diseases.

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When will clinical trials involving animal to human transplantation be permitted in Australia

NHMRC has recommended that clinical trials involving xenotransplantation could proceed in Australia when the following conditions are in place:

  • The Therapeutic Goods Administration has implemented a robust framework to regulate clinical trials involving xenotransplantation;
  • An appropriate standard of oversight and monitoring is established, including for example, a surveillance strategy and a patient registry; and
  • NHMRC has issued, using the advice of its Australian Health Ethics Committee and Animal Welfare Committee, guidance for researchers and ethics committees involved in animal to human studies.
As the processes described above will require collaboration between a range of organisations in addition to community consultation, it is difficult to propose an accurate time frame in which these processes may be complete. However, it is expected that it will take more than one year.  

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Are animal to human transplantation clinical trials permitted elsewhere in the world?

Yes. Many countries have decided to allow animal to human transplantation clinical trials. Included in this list is New Zealand, USA, Mexico, Russia, Germany, Switzerland, Malaysia, Ukraine, Sweden, France, Italy and China.

NHMRC is aware of two clinical trials involving animal to human transplantation currently underway outside Australia. One is in Russia and the other is in New Zealand. Both trials involve the transplantation of DIABECELL® into consenting patients with poorly controlled type 1 diabetes. DIABECELL® is a pancreatic product containing insulin producing (islet) cells harvested from pigs specifically bred for this purpose. The purpose of the cells is to release insulin into the patient’s body in response to elevated glucose levels. The cells are surrounded by a capsule to protect it from the patient’s immune system and prevent the patient’s body rejecting the transplant.

In other clinical trials (performed outside Australia) researchers have transplanted pig nerve cells into consenting patients for the treatment of Parkinson’s disease and Huntington’s disease, and used pig livers to filter blood while patients await a human liver transplant.

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Why is xenotransplantation being considered?

Transplantation between members of the same species is known as allotransplantation, and in humans this is a very successful way to treat a variety of illnesses. However, few human tissues, cells or organs are available for transplantation, so that many patients who could benefit from a transplant wait in vain for a suitable donor. Transplant specialists are therefore considering animals as possible donors for human transplantation. The greatest benefit of animal to human transplantation would be a potentially unlimited supply of cells and tissues for use in humans.

Organ transplants are the most complicated type of xenotransplantation because unlike cells and tissues, organs require lots of blood vessels to supply the organ with oxygen and nutrients. Some researchers are looking at temporarily transplanting pig livers into humans who have liver failure. Some patients with liver failure need to undergo urgent liver transplants, usually within 24 to 36 hours. If a compatible human liver is not transplanted within this time, the patient may become too ill for surgery. A temporary liver transplant would keep the patient alive until a suitable human liver can be found. This procedure is known as a ‘bridging transplant’. It is unlikely that permanent animal-to-human transplantation with organs will take place for many years.

Recent advances in technology have increased the possibility of successful animal to human transplantation and stimulated research in this area. For example, genetic engineering has allowed human genes to be inserted into pigs so that their cells, tissues and organs are less likely to be rejected when transplanted into humans. More knowledge of medicine can be gained through xenotransplantation research. This knowledge can in turn improve a range of medical technologies, not just xenotransplantation.

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What sort of disease or health problems could xenotransplantation help to cure or alleviate?

Animal to human transplantation has the potential to treat a wide range of life-threatening or debilitating conditions. For example, it is possible that isolated cells could be transplanted to treat diseases such as diabetes, Parkinson's disease, Huntington's disease or strokes.

Another possibility is that animal to human transplantation could be used to 'buy time' while potential transplant patients wait for a suitable donor. There have been promising results from overseas trials in which isolated pig liver cells were used to treat patients with acute liver failure. These cells were housed in a specially designed unit. When blood was passed through the unit, the cells filtered the blood, functioning as a liver would.

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What does xenotransplantation research involve?

In order for xenotransplantation to become an option for human therapy, research is needed that includes:

  • animal-to-animal studies (preclinical studies) - in which proposed xenotransplantation procedures are tested on animals (eg pig-to-baboon kidney transplant); and
  • animal to human trials (clinical trials) - in which animal products are used for xenotransplantation procedures on human beings (eg pig-to-human pancreatic islet cell transplantation to treat Type I diabetes).

Animal-to-animal studies are required to abide by regulations for research involving animals.

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Which animals are suitable donors for humans?

Pigs are considered the most suitable species as a source of material for animal to human transplantation for several reasons:

  • they reproduce quickly and have large litters;
  • their organs are similar in size to those of humans;
  • they are easy to breed;
  • there is less risk (when compared with apes and monkeys) that they will carry diseases that can infect humans;
  • their genes can be manipulated to reduce the risk of rejection from the human body.

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Have humans been transplanted with animal cells, tissue or organs?

Yes. Outside of Australia, over 200 people have been exposed to pig cells and tissues through animal to human transplantation. Early attempts at animal to human transplantation were not very successful. Over the last few decades, researchers have gained a better understanding of the science and outcomes have improved significantly.

In clinical trials (performed outside Australia) researchers have transplanted pig nerve cells into consenting patients for the treatment of Parkinson’s disease and Huntington’s disease, and used pig livers to filter blood while patients await a human liver transplant. Insulin producing cells (islets), taken from the pancreas of pigs have been transplanted into consenting patients to treat type 1 diabetes

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What are the risks of xenotransplantation to the recipient?

Undergoing animal to human transplantation often involves surgery. Surgery is an invasive procedure and should never be perceived as an easy and risk free process. Complications may occur from the anaesthetic and risks of bleeding, infections and cardiac or breathing complications are possible.

The most significant risk to the recipient of a transplant is rejection due to the patient's immune response. In human-to-human transplantation (allotransplantation), rejection has been largely overcome by tissue matching of donors and recipients, and by giving the recipient medicines that suppress their immune system.

The risk of rejection in animal to human transplantation is more complicated because the differences between the donor and the recipient are much greater. Two promising approaches have been developed. One is to modify the genetic makeup of the donor animals so that the cells and tissues do not trigger such a strong immune response from the human body. Scientists have already produced several genetically modified strains of pig that show promising results. Another is to protect cells from the immune system by applying a protective coating to the cells. This technology is known as ‘encapsulation’.

Other risks include the possibility of a virus being transmitted across species. Nonhuman primates (apes and monkeys) are not being considered as donors for animal to human transplants because their close relationship to humans increases this risk.

What viruses are we most concerned about in xenotransplantation?

A number of viruses exist in animal populations and it is possible that these could be introduced into the human population through animal to human transplantation. However, research over the last 5 years has shown us that by applying strategies, the risk can be minimised significantly.

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.

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Are there any risks of xenotransplantation to the wider community?

Animal to human transplantation carries some risk for the wider community, although it is believed the risk is very small. The concern for public health is that xenotransplantation might transmit an infectious agent (such as a virus) from animals to humans causing disease. The new disease could also spread to those in close contact with the transplant recipient and the wider community.

The knowledge driving this concern is many past examples of retroviruses moving from one species to another. Retroviruses do not always cause obvious signs of disease immediately. Therefore, if a retrovirus in a xenotransplant were to infect the recipient of the transplant, it may spread to close contacts, carers and even the general population before it became obvious that an infection had occurred.

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What steps would be taken to minimise the risks from xenotransplantation?

If animal to human trial were allowed in Australia, animals would be bred in compliance with strict policies and testing the donor tissue for bacteria, viruses and disease would be mandatory.

Although most pigs carry PERV, there are strains of pigs that do not carry the virus. Researchers are likely to use these strains (or breed others) for animal to human transplantation to further reduce the risk of infection in the recipient.

Animal to human trials will not be permitted unless there is an appropriate infection control policy in the hospital where the transplant is taking place, to prevent transmission of infections from the xenotransplant recipient to hospital contacts. In addition, because the long-term consequences of xenotransplantation will not be fully understood for some years, anyone transplanted with cells, tissues or organs from another species will need to be carefully monitored. Therefore, anyone receiving a transplant would be informed about the potential infectious disease risks to themselves and their close contacts and asked to support such long-term monitoring.

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Who would be responsible for controlling xenotransplantation trials in Australia?

In Australia, permission must be sought from the Therapeutic Goods Administration before a clinical trial can commence. Trials involving new medical technologies undergo strict assessment and researchers need to demonstrate the potential benefit of the therapy outweighs the risk. Clinical trials also undergo ethical assessment by a committee of experts.

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Further information

For more information on the issues about animal to human transplantation see the overview of xenotransplantation.

» Return to the animal to human transplantation research page.

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