Just this year, back in March, Japan’s education and science ministry issued new guidelines allowing the creation of human-animal embryos that can be transplanted into surrogate animals and brought to term. Before that, Japan explicitly forbid the growth of animal embryos containing human cells beyond 14 days or the transplant of such embryos into a surrogate uterus.
Now with the ban lifted, the first person to receive government support is a Japanese stem-cell scientist, named Hiromitsu Nakauchi, who will create animal embryos that contain human cells and transplant them into surrogate animals. He currently leads teams at the University of Tokyo and Stanford University in California. To begin with, he and his colleagues will grow human cells in mouse and rat embryos and then transplant those embryos into surrogate animals. Nakauchi’s aim is to eventually produce animals with organs made of human cells that can be transplanted into people.
Nakauchi says he will not attempt to bring any hybrid embryos to term for some time. He plans to start slowly by initially growing hybrid mouse embryos until 14.5 days when the animal’s organs are mostly formed and it is almost to term. Then, he will do the same experiments in rats, growing the hybrids to near term, which is about 15.5 days. Only after those go well will he apply for government approval to grow hybrid embryos in pigs for up to 70 days.
Science-policy researcher Tetsuya Ishii of Hokkaido University in Sapporo, Japan, said: “It is good to proceed stepwise with caution, which will make it possible to have a dialogue with the public, which is feeling anxious and has concerns.”
There are some concerns among a few bioethicists regarding the possibility that human cells might stray beyond the development of the targeted organ, travel to the developing animal’s brain and potentially affect its cognition. However, according to Nakauchi, such concerns have been taken into consideration in the experiment design. “We are trying to do targeted organ generation, so the cells go only to the pancreas,” he said.
Nature explains the procedure as such:
The strategy that he and other scientists are exploring is to create an animal embryo that lacks a gene necessary for the production of a certain organ, such as the pancreas, and then to inject human induced pluripotent stem (iPS) cells into the animal embryo. iPS cells are those that have been reprogrammed to an embryonic-like state and can give rise to almost all cell types. As the animal develops, it uses the human iPS cells to make the organ, which it cannot make with its own cells.
A 2017 study by Nakauchi and his colleagues reported a successful procedure where they injected mouse iPS cells into the embryo of a rat that was unable to produce a pancreas. The rat was able to form a pancreas made entirely of mouse cells. Nakauchi and his team then transplanted that pancreas back into a mouse that had been engineered to have diabetes. The rat-produced organ was able to control blood sugar levels, thus effectively curing the mouse of diabetes!
Although getting human cells to grow in another species is not as easy, Nakauchi and colleagues have already made one attempt by putting human iPS cells into sheep embryos that had been engineered not to produce a pancreas. In the end, the hybrid embryos, grown for 28 days, contained very few human cells, and nothing resembling organs they announced at the 2018 American Association for the Advancement of Science meeting in Austin, Texas. Nakauchi said the failure was probably due to the genetic distance between humans and sheep.
“Understanding the molecular basis and developing strategies to overcome this barrier will be necessary to move the field forward,” said Jun Wu, who researches human-animal chimeras at the University of Texas Southwestern Medical Center in Dallas. It doesn’t make sense to bring human-animal hybrid embryos to term using evolutionarily distant species like pigs and sheep because the human cells will be eliminated from host embryos early on.
Nakauchi is taking on the challenge of attacking this problem with full-hearted enthusiasm. He plans on experimenting with iPS cells at subtly different stages and trying some genetically modified iPS cells to try to determine what limits the growth of human cells in animal embryos.
