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Organ research scientists combine human stem cells and pig DNA

by Kevin Rawlinson & Nicola DavisThe Guardian
June 6th, 2016

Image of a pig with its head pointed upwards.

Scientists trying to grow human organs inside pigs in an attempt to tackle a shortage of donors have successfully created part-human, part-pig embryos.

Researchers at the University of California, Davis combined human stem cells and pig DNA and allowed the embryos to mature for 28 days, before terminating the experiment and analysing the tissue.

They believe the animals, which if they had been carried to term would have developed a human internal organ, but would have looked and behaved like any other pig. The goal is that in the future, similar animals could potentially act as a ready source of organs for life-saving transplants.

To create the “chimeric” embryos, the scientists used a gene-editing technique known as Crispr to knock out a section of the pig’s DNA necessary for the embryo to develop a pancreas.

Human induced pluripotent (iPS) stem cells were then injected into the pig embryo. These are cells that have the potential to develop into any tissue type in the resulting foetus. Although genetically foreign, they are not rejected by the pig embryo because its immune system has not yet developed.

Instead, the human cells would be expected to follow the chemical cues from the pig embryo to develop into different tissues in the foetus. In most cases they are outcompeted by the pig embryo’s own cells but in the case of the pancreas there are no pig cells to compete with. Hence the embryo goes on to develop a pancreas derived from the injected human cells.

“You are basically creating a vacuum, a hole, so that the human cells respond to the right cues, they make a pancreas. The pig cells can’t. But what we don’t know, and this is what they need to look at, is whether the human cells can also contribute substantially to other tissues, and particularly they are worried about the brain,” said Robin Lovell-Badge, a geneticist at the Francis Crick Institute in London.

It was reported earlier this year that scientists had begun attempts to create the embryos, but there has been opposition from authorities. In September last year, the US National Institutes of Health said it would not back research into “chimeras” until it knew more about the implications.

It cited fears that the presence of human cells could affect the animal’s brain and behaviour, potentially making it more human. Prof Pablo Ross, the reproductive biologist leading the research, sought to calm those fears, saying there was a “very low potential for a human brain to grow”.

“Our hope is that this pig embryo will develop normally but the pancreas will be made almost exclusively out of human cells and could be compatible with a patient for transplantation,” he said.

The approach is not without potential problems. “There are other cells types that are going to be present in the pancreas which come from the pig – that would include blood vessels,” said Lovell-Badge. “Those would be a big problem and they would be rejected by a human.” It is also possible that the surface of the human cells may be modified inside the pig embryo, potentially leading to the organ being rejected by a human.

Concerns have been raised about whether the transplantation of an organ from an animal into a human could risk introducing animal viruses into a patient. Researchers from Harvard Medical School, however, revealed last year that it was possible to use gene-editing technology to inactivate more than 60 retrovirus genes in pigs in a step towards such organ transplantation.

It is not the first attempt to create chimeras. Among the previous experiments, scientists using different techniques were able to produce a mouse with a rat’s pancreas, and mice with livers almost completely composed of human cells.

“The whole idea of making chimeras, mixing different animal species or human-animal, has been around for decades,” said Lovell-Badge.

But Peter Stevenson, from Compassion in World Farming, told the BBC’s Panorama programme: “I’m nervous about opening up a new source of animal suffering. Let’s first get many more people to donate organs.

“If there is still a shortage after that, we can consider using pigs, but on the basis that we eat less meat so that there is no overall increase in the number of pigs being used for human purposes.”

A pig was said to be an “ideal incubator” for human organs and Walter Low, a professor in the department of neurosurgery, University of Minnesota, told the BBC that researchers wanted to create not just a pancreas – the current focus – but also hearts, livers, kidneys, lungs and corneas.

Prof George Church, who has led similar research into the possible use of chimeras, told the broadcaster: “It opens up the possibility of not just transplantation from pigs to humans but the whole idea that a pig organ is perfectible.

“Gene editing could ensure the organs are very clean, available on demand and healthy, so they could be superior to human donor organs.”

Image via Pixabay



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