Hiromitsu Nakauchi, who leads teams at the University of Tokyo and Stanford University in California, plans to grow human cells in mouse and rat embryos and then transplant those embryos into surrogate animals.
While many countries around the world have restricted, defunded or outright banned these ethically-fraught practices, Japan has now officially lifted the lid on this proverbial Pandora’s box. Earlier this year, the country made it legal to not only transplant hybrid embryos into surrogate animals, but also to bring them to term.
According to Nature, Nakauchi is the first stem-cell scientist to receive government funding from Japan to conduct human-animal embryo experiments. The ultimate goal is to create animals with organs that could feasibly be transplanted to people.
As one would expect, there have been numerous ethical concerns regarding the process, such as the possibility that human cells might stray beyond the intended organ and travel to the developing animal’s brain, potentially affecting its condition.
Nakauchi says he plans to proceed slowly, and will not attempt to bring any hybrid embryos to term for some time. Initially, he plans to grow hybrid mouse embryos until 14.5 days, when the animal’s organs are mostly formed and it is almost to term. He will do the same experiments in rats, growing the hybrids to near term, about 15.5 days. Later, Nakauchi plans to apply for government approval to grow hybrid embryos in pigs for up to 70 days.
“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,” says science-policy researcher Tetsuya Ishii of Hokkaido University in Sapporo, Japan.
Allaying the concerns, Nakauchi said:
Human-animal hybrids have been produced in the US, where rules are more relaxed – though the National Institutes of Health has had a moratorium on funding this type of work since 2015.
However, until March this year, Japan explicitly forbid the growth of animal embryos containing human cells beyond 14 days or the transplant of such embryos into a surrogate uterus.
Nakauchi’s plans are the first to be approved under Japan’s education and science ministry’s new guidelines, which allow the transplant of embryos into surrogate animals.
Jun Wu, who researches human–animal chimaeras at the University of Texas Southwestern Medical Center in Dallas, said this is an essential step in the exploring evolution.
Jun Wu said:
Understanding the molecular basis and developing strategies to overcome this barrier will be necessary to move the field forward.
Nakauchi and his colleagues reported in 2017 the injection of mouse iPS cells into the embryo of a rat that was unable to produce a pancreas. The rat formed a pancreas made entirely of mouse cells. Nakauchi and his team 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, effectively curing the mouse of diabetes.
Nakauchi says the approval in Japan will allow him to attack this problem. He will be 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.
Photos: Google images