Cynomolgus monkey cells were genetically modified growing in culture to produce a fluorescent GFP protein, this enabled cells to be tracked and their descendents; embryonic stem cells were then derived from the modified cells which were injected into pig embryos 5 days after fertilization. Over 4000 embryos were implanted into sows, 10 piglets were born as a result two of which were chimeras; all died within a week with the chimeric pigs having multiple issues including in the liver, lungs, spleen, skin, and heart.
According to Hai it is not clear why exactly the piglets died because even the non-chimeric piglets died as well, it is suspected to have something to do with the IVF process rather than the chimerism as IVF does not work as well in pigs as it does in humans and some other animals.
Using a greater proportion of monkey cells the scientists are now working to create healthy animals, if successful the next step could be attempting to create a pig-monkey chimera in which one organ is composed almost entirely of primate cells. Hiromitsu Nakauchi achieved something similar to this in 2010 by creating mice with rat pancreases via genetically modifying mice so their cells could not develop into a pancreas.
The ultimate goal of this work is to be able to grow human organs in animals to use for transplantation, to which the team says there is still a long way to go before being able to achieve this.
At the Salk Institute in 2017 Juan Carlos Izpisua Belmonte and colleagues created pig-human chimeras with low proportions of 1 in 100,000 cells being human, for ethical reasons theses embryos were only allowed to develop for one month due to concerns that a chimera brain could have been partly human. A report in El Pais suggests that this team has now created a human-monkey chimera working in China, but there have been no published reports.
Hai and colleagues used monkey cells rather than human cells for this ethical reason, while the proportion of monkey cells in their chimeras were higher than what was used in Belmonte’s the proportion was 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 who is not convinced that it will ever be possible to grow organs that will be suitable for human transplantation uses in this manner; but he does say it still does make sense to continue researching.
Interspecies chimerism does not occur naturally, but bodies of animals and humans can consist of a mix of cells, such as mothers can have cells from their children growing in their organs in a phenomenon called microchimerism.
