What is xenotransplantation?

Xenotransplantation is when cells, tissues, or organs are taken from one species and put into another. For example, pig organs have been used to replace diseased organs in humans, and pig brain cells have been used to replace missing cells in patients suffering from Parkinson’s disease.

Why use xenotransplantation?

Sometimes the only cure for someone very sick with diseases such as kidney or liver failure is for them to have a transplant. However, Organ Donation New Zealand says that there are always more people waiting for organ transplants than the number of organs available for transplantation. Because more people are living longer, this need is only likely to increase.

Could using organs from other species help address the gap between the number of people needing organs and the number of organs available?

What animals could be used?

Some primates, such as chimpanzees, are very similar to humans. This includes the structure and size of most of their vital organs, making them possible candidates for organ donors. However, the similarities also mean that there is a greater risk that primate diseases might cross the species barrier and affect humans.

Pigs are the current preferred donor species. Their organs are also a similar size to human organs, and they have large litters that are relatively easy to rear in pathogen-free conditions.

Organ rejection

Piglets

One of the biggest problems with transplants of any kind is rejection.

The human body has a highly developed immune system, which specialises in recognising and attacking foreign cells and tissues. This immune response helps us to fight infections and stay healthy, but it also causes attacks on transplants and can result in donated tissue being ‘rejected’.

Preventing organ rejection

The risk of rejection is reduced if the transplant tissues match the host tissues as closely as possible. In other words, the donor and recipient must share most of the same characteristics, such as blood type and Rhesus factor.

Liver

A donor animal will never be a perfect match for a human.

Immunosuppressive drugs can be used to reduce the ability of the immune system to attack transplanted cells, but these drugs also reduce the immune system’s ability to fight off other infections. They are also not a guarantee of success – even when these drugs are used, some xenotransplants have been rejected by a recipient’s body.

Current research on xenotransplantation is focusing on making the transplanted tissue unrecognisable to the immune system. There are two main ways to ‘hide’ transplant tissue from the immune system:

An invisibility cloak for cells

New Zealand company Living Cell Technologies has developed a technology where cells are hidden from the immune system by an algae-based coating. This coating acts like an invisibility cloak and prevents cell rejection by the patient’s immune system without using toxic drugs.

Cells in disguise

Using modern DNA technologies, cells can be genetically engineered to produce proteins that trick the recipient’s immune system into thinking it is part of their own tissue; the immune system will not recognise the tissue as foreign and will leave the tissue unharmed. For example, adding one specific human gene to the pig genome causes the pig cells to produce a human protein on the surface of their internal organs.

A PERVy problem

Another risk of xenotransplantation is that pathogens from the donor species may infect the recipient. For example, many pigs carry a virus called porcine endogenous retrovirus (PERV).

A trial in which pig cells were transplanted into a diabetic mouse found a PERV had infected the mouse. However, none of the 200 patients who received pig xenotransplants during trials overseas in the 1990s has become infected with PERVs.

If PERVs were to cross the species barrier into humans and then become more contagious by a series of mutations, many humans could be affected.

Xenotransplantation in New Zealand

Scientists in New Zealand are in the lucky position of having a virus-free population of pigs to work with – whalers established a pig population on the remote Auckland Islands as a food source in 1807. This pig population has been isolated from other pigs ever since and is completely free of disease.

In 1996, Living Cell Technologies ran a clinical trial where insulin producing pig cells were injected into people with type I diabetes, but this was stopped when xenotransplant research was halted throughout the world while more testing was carried out to assess the risks of xenotransplantation.

In 2005, the New Zealand government recommended that xenotransplantation should proceed on a case-by-case basis. Since then, Living Cell Technologies have applied for approval to run a clinical trial treating eight diabetics with insulin-producing pig cells.

Get news story: Pig cell trial to start

What are the alternatives?

Some conditions that require a transplant are brought about by lifestyle. For example, heart transplants are often required by people who have damaged their hearts through poor diet, insufficient exercise, and/or smoking. Perhaps if people had healthier lifestyles, the demand for donors would decrease?

The short-fall in human donors could also be addressed by increasing the number of willing donors. But how do you do this, and will it be enough?

Mechanical artificial body parts may provide alternative solutions to some disorders currently requiring a transplant. Pacemakers are a very successful example of this.

Finally, stem cell research might find ways to replace more complex tissues, although many people still consider this work to be highly controversial.

See the video conference Body invaders to the rescue

A Biotech Hub video conference with intermediate school students, featuring:

• Xenotransplantation: What is it?
• Xenotransplantation saves Jim
• Xenotransplantation saves Robert
• Xenotransplantation: Would you do it?

Get video conference: Body invaders to the rescue

Written by Sara Loughnane, NZ Science, Mathematics, and Technology Teacher Fellow, 2006.