First human-sheep hybrids created

Organs to be grown in animals for transplant, provide cure for diabetes
Scientists have created the first ever human-sheep hybrids, paving the way for organs to be grown in animals which can be transplanted into humans.

The successful Stanford University project could even open the door to finding a cure for type 1 diabetes by creating healthy pancreases to regulate blood sugar.

While scientists have previously developed human-pig hybrids, sparking excitement that they could use them grow human organs, no team has been able to take it to the next step.

But Stanford’s team, which has already successfully transplanted pancreases into mice, is tipped to be the first after now that they have produced a human-sheep model to use.

“We have already generated a mouse pancreas in rats and then transplanted those in to diabetic mouse and were able to show almost a complete cure,” project lead Dr Hiro Nakuachi, a professor of genetics at Stanford, told the American Association for the Advancement of Science conference.

“It could take five years or it could take 10 years but I think eventually we will be able to do this.”

The breakthrough could also help to alleviate the global shortage of organ donors.

Around 76,000 people in the US and 6,500 in the UK are on an organ transplant list, and it can take up to five years to reach the top.

The development comes less than two years after the US government said it would approve funding of these controversial experiments, but later backtracked after receiving more than 20,000 complaints from animal rights groups.

Pablo Ross, associate professor of animal science at the University of California, Davis who is part of leading the venture, admitted he harbors similar concerns.

It depends on how far the human cells roam in the animal, he said. If they spread further than intended, it could be impossible to approve for ethical reasons.

But he insisted it is one of the most promising explorations in medicine right now.

“We have this amazing life-saving technology right now [with organ transplantation] but there aren’t enough for everybody,” said Pablo Ross, associate professor of animal science at the University of California, Davis.

“Imagine you could grow organs in nine months to an adult size.”

We could even reach a point, he says, when these organs aren’t just used to save lives but that they could circumvent other conditions like diabetes.

Transplanting organs from pig or sheep directly to humans has not been successful but researchers believe using human stem cells may be an alternative solution.

Researchers have previously developed human-pig hybrids but have not yet been able to use the process to grow human organs

To create their ‘chimera’ – as hybrid animal-humans are called – the team grew embryos containing sheep and human cells, and kept the surrogate animal carrying them alive for three weeks.

The team now plans to implant human stem cells into sheep embryos and hope that human Deoxy ribonucleic Acid (DNA)/genetic material will be able to grow organs such as a pancreas. It would be a world first if a human organ could be grown inside a sheep.

Last year, mouse pancreases were grown inside rats – a first step towards a ready supply of organs for transplant.

When small parts of these organs were transplanted into mice with diabetes, it reversed their disease. This finding raises the prospect that someone needing a new liver, for instance, could have what is essentially their own organ grown to order inside a specially conceived piglet, within a year of providing a small skin sample. Pigs or sheep make the best candidates, because their organs are a similar size to ours.

Donor organs shortage has prompted research into creating organs in the lab. Many of these methods involve stem cells, which can be encouraged to form most types of tissue using different mixtures of chemical cues and signalling molecules. However, growing large organs with complex three-dimensional structures and their own blood supply has proved far from easy.

Instead, Hiromitsu Nakauchi at the University of Tokyo, Japan, and his team used rat embryos as living incubators. They began by genetically modifying parent rats so their offspring would be unable to make their own pancreas. A few days after conception, they injected mouse stem cells into the tiny rat embryos, which developed as normal, except their pancreases mostly comprised mouse cells.

Once the rats reached adulthood, the team removed the pancreases and implanted clusters of these pancreatic cells into mice with diabetes. These clusters, or islets, restored the blood glucose levels of the mice to normal for over a year.

This was the first time this kind of inter-species organ generation has successfully treated a medical condition. “It proved those pancreatic islets must be very functional,” said Nakauchi.

“This is the first time this kind of inter-species organ generation has treated a medical condition”

That doesn’t mean doing the same with whole organs in pigs and people is imminent, though. The team used clusters of cells, instead of transplanting whole pancreases, partly because the procedure is relatively easy.

As humans and pigs are less genetically similar than rats and mice, the growing organ might be attacked by the piglet’s immune system. The team found that the islet clusters contained some rat cells from other tissues, but that the mouse immune system seemed to kill these without harming the pancreas cells. However, this may be more dangerous if a whole, large organ is transplanted.

While the approach was used to cure mice with diabetes, people can already be treated with insulin. So the technique may prove more important for treating other diseases. New organs are more urgently needed for people with failing hearts, livers, lungs and kidneys, said Nakauchi.

So far, his team has managed to modify rats so they don’t grow a liver, so it should be possible to grow mouse liver cells for transplant in a similar way to the islet cells. But getting rid of the heart is likely to be more difficult, he said.

There are also ethical issues. Because the technique would involve inserting human cells into pig embryos, the adult animals could have some human brain cells. Does that mean we should give those pigs greater moral consideration?