By Michael Le Page

Tang Hai

Pig-primate chimeras have been born live for the first time but died within a week. The two piglets, created by a team in China, looked normal although a small proportion of their cells were derived from cynomolgus monkeys.

This is the first report of full-term pig-monkey chimeras, says Tang Hai at the State Key Laboratory of Stem Cell and Reproductive Biology in Beijing.

The ultimate aim of the work is to grow human organs in animals for transplantation. But the results show there is still a long way to go to achieve this, the team says.

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Hai and his colleagues genetically modified cynomolgus monkey cells growing in culture so they produced a fluorescent protein called GFP. This enabled the researchers to track the cells and their descendents. They then derived embryonic stem cells from the modified cells and injected them into pig embryos five days after fertilisation.

More than 4000 embryos were implanted in sows. Ten piglets were born as a result, of which two were chimeras. All died within a week. In the chimeric piglets, multiple tissues including in the heart, liver, spleen, lung and skin partly consisted of monkey cells, but the proportion was low: between one in 1000 and one in 10,000.

It is unclear why the piglets died, says Hai, but because the non-chimeric pigs died as well, the team suspects it is to do with the IVF process rather than the chimerism. IVF doesnt work nearly as well in pigs as it does in humans and some other animals.

The team is now trying to create healthy animals with a higher proportion of monkey cells, says Hai. If that is successful, the next step would be to try to create pigs in which one organ is composed almost entirely of primate cells.

Something like this has already been achieved in rodents. In 2010, Hiromitsu Nakauchi, now at Stanford University in California, created mice with rat pancreases by genetically modifying the mice so their own cells couldnt develop into a pancreas.

In 2017, Juan Carlos Izpisua Belmontes team at the Salk Institute in California created pig-human chimeras, but only around one in 100,000 cells were human and, for ethical reasons, the embryos were only allowed to develop for a month. The concern is that a chimeras brain could be partly human.

This is why Hai and his team used monkey rather than human cells. But while the proportion of monkey cells in their chimeras is higher than the proportion of human cells in Belmontes chimeras, it is still very low.

Given the extremely low chimeric efficiency and the deaths of all the animals, I actually see this as fairly discouraging, says stem cell biologist Paul Knoepfler at the University of California, Davis.

He isnt convinced that it will ever be possible to grow organs suitable for transplantation by creating animal-human chimeras. However, it makes sense to continue researching this approach along with others such as tissue engineering, he says.

According to a July report in the Spanish newspaper El Pas, Belmontes team has now created human-monkey chimeras, in work carried out in China. The results have not yet been published.

While interspecies chimerism doesnt occur naturally, the bodies of animals including people can consist of a mix of cells. Mothers have cells from their children growing in many of their organs, for instance, a phenomenon called microchimerism.

Journal reference: Protein & Cell, DOI: 10.1007/s13238-019-00676-8

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