Growing human organs inside other animals has taken another step away from science-fiction, with researchers announcing they have grown sheep embryos containing human cells.
Scientists say growing human organs inside animals could not only increase supply, but also offer the possibility of genetically tailoring the organs to be compatible with the immune system of the patient receiving them, by using the patient’s own cells in the procedure, removing the possibility of rejection.
According to NHS Blood and Transplant, almost 460 people died in 2016 waiting for organs, while those who do receive transplants sometimes see organs rejected.
“Even today the best matched organs, except if they come from identical twins, don’t last very long because with time the immune system continuously is attacking them,” said Dr Pablo Ross from the University of California, Davis, who is part of the team working towards growing human organs in other species.
Ross added that if it does become possible to grow human organs inside other species, it might be that organ transplants become a possibility beyond critical conditions.
Bruce Whitelaw, professor of animal biotechnology at the Roslin Institute, where Dolly the sheep was created, said that while there was a long way to go before human organs could be grown in other animals, the latest research is “an important step forward through starting to explore whether sheep offer an option for the exciting ‘chimeric’ project.”
The approach is different to xenotransplantation, in which an organ that belongs to another species is transplanted into humans. While that is another possibility for tackling the dearth of organs, rejection would still be a problem.
Attempts by scientists to grow organs from one species inside another is an ongoing mission: among previous efforts, scientists have grown a rat pancreas inside a mouse.
But Ross and colleagues have recently reported a major breakthrough for our own species, revealing they were able to introduce human stem cells into early pig embryos, producing embryos for which about one in every 100,000 cells were human. These chimeras – a term adopted from Greek mythology – were only allowed to develop for 28 days.
Now, at this week’s meeting of the American Association for the Advancement of Science in Austin, Texas, the team have announced that they have managed a similar feat with sheep embryos, achieving an even higher ratio of human to animal cells. “About one in 10,000 cells in these sheep embryos are human,” said Ross.
The team say they have already been able to use genome editing techniques to produce pig and sheep embryos that are unable to develop a pancreas, although they are still working on the approach. The hope is that the human cells introduced to such embryos would grow to replace the missing organ.
The team are currently allowed to let the chimeric embryos develop for 28 days, 21 of which are in the sheep. While that might be sufficient to see the development of the missing organ when human cells are eventually combined with the genetically modified embryo, Dr Hiro Nakauchi of Stanford University, who is part of the team, said a longer experiment, perhaps up to 70 days, would be more convincing, although that would require additional permission from institutional review boards.
But, Ross said, for the approach to work it is thought that about 1% of the embryo’s cells would have to be human, meaning further work is needed to increase the proportion of human cells in the chimera.
Ross added there are several advantages to using sheep embryos, including that they can easily be produced by IVF, and that fewer embryos need to be transplanted into an adult, meaning fewer embryos are needed for an experiment.
“For a pig we typically transfer 50 embryos to one recipient,” said Ross. “With the sheep we transfer four embryos to one recipient.”
Sheep also have certain organs – such as the heart and lungs – that are similar to ours, and their embryos have been shown to form chimeras with goat embryos to produce “geeps”. Like pigs, sheep produce organs of about the right size for the human body.
Research with pigs is continuing, said Ross, noting that they have other benefits including speed of growth and the ability to produce more young at one time than sheep, meaning fewer animals are needed to produce more data.
But ethical concerns abound, not least whether chimeras could end up with a human-like mind.
“I have the same concerns,” said Ross, adding that the team are looking at where the human cells end up in the chimera. “Let’s say that if our results indicate that the human cells all go to the brain of the animal, then we may never carry this forward,” he said.
Nakauchi is optimistic that humans will eventually be able to receive organs grown in animals. “It could take five years or it could take 10 years but I think eventually we will be able to do this,” he said.
Nakauchi also played down concerns: “The contribution of human cells so far is very small. It’s nothing like a pig with a human face or human brain,” he said. “We have published several papers showing we can target the region, so we can avoid human cells differentiating in to the human brain or human gonads.”
Other potential issues includethat viruses within the DNA of the host could infect human cells, while the human organ might contain blood vessels composed of cells from the “host” animal. “The organs could not be used for transplants into humans without triggering the immune system to reject them – and this would probably be a very fast rejection,” said Robin Lovell-Badge, head of the division of stem cell biology and developmental genetics at the Francis Crick Institute in London.
However, recent developments in gene editing have allowed scientists to develop piglets without such viruses, potentially smoothing the way, while Ross notes that human cells might replace any remaining host cells after transplantation.
Currently, the US National Institutes of Health has a moratorium on funding such research, but it is looking to lift this and replace it with a review process. In the UK scientists must apply to the Home Office for a license to carry out such research.