The cells most likely to be used first are islet cells from the pancreas, which produce insulin and could be transplanted to help some people with type 1 diabetes to regulate their blood sugar.
The islet cells in people with type 1 diabetes have been destroyed and no longer produce insulin.
“The reason there’s a bit of action going on at the moment is that pancreatic islet transplantation has now entered the clinical trial stage.” — Peter Cowan, of St Vincent’s Hospital
The use of pig or other animal organs and tissue as transplants for humans, a field known as xenotransplantation, has long been a prized goal of medical science, although the issue has received little recent media coverage.
But Professor Peter Cowan, of Melbourne’s St Vincent’s Hospital, says progress in xenotransplantation has definitely accelerated over the last five years, with 2014 revealing the results of some key studies.
“The reason there’s a bit of action going on at the moment is that pancreatic islet transplantation has now entered the clinical trial stage,” he said.
A huge hurdle for xenotransplantation has been the possibility of infectious agents passing from pigs to humans, especially porcine endogenous retroviruses or PERVS.
Last year, New Zealand researchers reported a small clinical trial where pig islet cells were transplanted into people with diabetes. The specially housed pigs were not genetically modified and were rigorously screened for micro-organisms.
Professor Cowan said that this trial, and others, had found no evidence of PERVs or any other infections in the people who were treated.
“The PERV issue has almost become a non-issue now,” he said. “It’s been impossible to show that PERV infection will be a problem. Also, the screening of the pigs has improved enormously so you can now selectively breed pigs that are so-called low or non-transmitters of PERV.”
Xenotransplantation is one of a number of possible approaches to overcoming the shortage of human tissues and organs available for transplants.
Melbourne has a strong history of xenotransplantation research over 25 years, and Professor Cowan’s group at St Vincent’s and another based at Austin Health are still strong contributors to the field.
Progress in most areas of research has its highs and lows. But after the heady days of the 1990s, xenotransplantation hit a perfect storm of negative issues around the turn of the millennium.
Improving access to transplant organs
- Transplants from living family members
- ‘Daisy chain’ transplants – for example, one altruistic kidney donor can lead to a 10-way swap of kidneys to give best possible matches
- Transplants from donors with incompatible blood groups
- Xenotransplantation – transplants from genetically engineered pigs
- Transplants of organs/tissue grown from stem cells
- Short-term “bridging” transplants – to give patients time to wait for a more suitable transplant organ
Fear of PERVS exploded around 2000, as momentum in the field grew and xenotransplantation seemed closer to reality. When this fear was combined with the cost and difficulty of genetic engineering of pigs to avoid rapid rejection, xenotransplantation seemed too risky a venture for governments and investors. At the same time, stem cell research, in some ways a competing technology, hit the headlines as a potential way of supplying tissues and organs.
“I think most of the companies left the field [of xenotransplantation] so a lot of the support dropped, the financial support, the research support. It was difficult to continue to research at that time,” Professor Cowan said.
The Australian National Health and Medical Research Council imposed a five-year moratorium on clinical xenotransplantation in 2004, but this was lifted in 2009 under strict conditions.
Associate Professor Bruce Loveland, now at the Burnet Institute in Melbourne, was previously the head of an Austin team that worked in the field. He thinks xenotransplantation can still contribute to the shortage of tissues for transplant.
“If you look at the options for patients now compared to 10 years ago, 20 years ago, the options are much better than they were, but there are still big gaps. So the interest in xenotransplantation is there.”
He noted a clinical program at St Vincent’s was also researching human islet cell transplants for people with diabetes. But even if ultimately successful, the lack of availability of human islet cells underscored the interest in islet cells from pigs.
“If you look at the options for patients now compared to 10 years ago, 20 years ago, the options are much better than they were, but there are still big gaps. So the interest in xenotransplantation is there.” — Bruce Loveland, of the Burnet Institute
Another researcher at University of Melbourne at Austin Health, Professor Mauro Sandrin, said that although there had been little recent public focus on xenotransplantation, the science and technologies had progressed, with cloning of animals now faster, cheaper and more precise.
“The time from cloning Dolly the sheep [the first animal cloned in 1996] to cloning a pig was six or seven years, or more. Now, if you Google ‘cloning of pigs’ there are stacks of articles.”
Professor Sandrin said the human body would usually reject a pig organ in minutes, a reaction called hyperacute rejection, but the technologies were now at a point where a pig heart transplant could keep a monkey alive for months.
“Progress has been made in clinical models where we’ve got life-supporting kidneys going out beyond a year, life-supporting pancreatic islets going out beyond a year with immunosuppressive protocols that are probably clinically applicable [to humans].”
To date, a pig-to-human transplant of living organs or cells has not been performed in Australia, but if researchers could justify using pig transplants and meet the regulations, xenotransplantation could go ahead.
Professor Cowan, who is also president-elect of the International Xenotransplantation Association (IXA), says the World Health Organisation and the IXA have kept an eye on progress and have re-visited the guidelines for islet cell xenotransplantation to ensure the field is regulated.
He said there were few recent studies about attitudes to xenotransplantation, although pig (and cow) heart valves have been used routinely to repair human hearts for many years.
“I think very few people would think twice about getting a pig heart valve. If you told them that this is going to work better than a mechanical valve, then they’re going to take it.”
However, acceptance of xenotransplantation of living organs or cells could take a bit more time.
“In my opinion, you’ve got to get it into the clinic and show that it works and then I think people are going to accept it,” he said. “Until it really gets to the clinic in a big way, people probably still see it as too experimental.”
► This story was also published in The Sunday Age.