Scientists make human-sheep chimera more human than pig chimera

Modified pig embryo and sheep

Scientists have fine-tuned the technique to grow human organs within animals, this time using sheep instead of pigs.

Following the work with pigs last year that resulted in pigs with 0.001% human cells. This year the same team have developed a human-sheep chimera with 0.01% human cells, a percentage 10x higher.

Not only is the percentage higher, but the scientists used the genetic modifying technology CRISPR to disable pathways for specific organs such as the heart and liver so they wouldn’t develop. The sheep embryos were then injected with human stem cells which started specializing to form the missing organs. They say the work is being duplicated in pigs.

Every 10 minutes another person is added to the national waiting list for organ transplants in the United States. Every day 22 people on that list die waiting for an organ that they need. The team is trying to counter this problem by increasing the supply of available human-compatible organs.

Scientists say that growing organs inside animals could not only increase the supply but also decrease the likelihood of rejection, as the organs would be genetically tailored to be compatible with the immune system of the patient receiving them, by using the patient’s own cells in the procedure.

“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.

Although this research could lead to an increased supply of human-compatible and long-lasting organs for transplant patients, it doesn’t come without risk.

Creating human-sheep chimera embryos

There is the possibility that viruses within the host animal’s DNA could infect human cells. However, recent developments in gene editing have allowed scientists to develop piglets without these viruses. This would, however, require more genetic modification.

The scientists still claim that the organs would need to be at least 1% for transplantation into a human being, however, more research needs to be done to ensure that this is correct and to reach 1% human cells within host embryos.

The embryos have only been allowed to grow for up to 28 days, 21 days of which are within the sheep. This is enough time to see that the human cells start to develop the missing organs, but 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 permissions from institutional review boards.

There are several advantages to using sheep embryos over pig embryos, including that they can be easily produced using IVF. “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 heart and lungs that are similar to human organs, however, pigs have the benefits of speed of growth and the ability to produce more young at one time than sheep.

Both animals produce organs about the right size for the human body.

The team also aims to tackle some of the ethical concerns of the research when it comes to the animals possibly developing human-like minds or reproductive organs.

“I have the same concerns,” said Ross, adding that the team are looking at where the human cells end up. “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 commented on the ethical 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 into the human brain or human gonads.”

While this research currently requires a host embryo and host mother for the embryo, it could lead to organs being developed in the future without any animal host at all.

Commenting on the various methods scientists are trying to develop human-suitable organs, Ross sees the ever-widening approaches a cause for optimism. “All of these approaches are controversial, and none of them are perfect, but they offer hope to people who are dying on a daily basis,” he said. “We need to explore all possible alternatives to provide organs to ailing people.”

The team has not yet published a paper of their efforts but gave a presentation outlining their research efforts at this year’s American Association for the Advancement of Science meeting in Texas.

Currently, the US National Institutes of Health doesn’t allow public funding for such research, but it is looking to lift this and replace it with a review process.