Human (red) cells study a monkey embryo grown in the laboratory.
Weizhi Ji / Kunming University of Science and Technology
By Mitch Leslie
By straining human stem cells into the embryos of other animals, we could one day grow new organs for people with hesitant hearts or kidneys. In a step towards this goal, the researchers created the first embryos with a mixture of human and monkey cells. These chimeras could help scientists perfect techniques for growing human tissue to more suitable species for transplants, such as pigs.
“Paper is a landmark in stem cell fields and interspecies,” says stem cell biologist Alejandro De Los Angeles of Yale University. The findings indicate the mechanisms by which the cells of one species can adapt to survive in the embryo of another Daniel Garry, a stem cell biologist at the University of Minnesota (UM), Twin Cities.
In 2017, researchers reported the growth of pancreas from the stem cells of mice inserted into rat embryos. Organ transplantation in diabetic mice eliminated the disease. But cells from more distantly related species, such as pigs and humans, did not get along as well. In the same year, developmental biologist Juan Carlos Izpisúa Belmonte of the Salk Institute for Biological Studies and colleagues reported injecting human stem cells into pig embryos. After embryos developed in surrogate mother pigs for 3 to 4 weeks, only one in 100,000 of their cells was human.
The pig study used human skin cells that were reprogrammed into stem cells. But so-called extended pluripotent stem cells (EPS), made by exposing stem cells to a particular molecular cocktail, can generate a greater variety of tissues. In the new study, Izpisúa Belmonte, breeding biologist Weizhi Ji of Kunming University of Science and Technology, and colleagues tested those more capable cells in a closer human relative – the cynomolgus monkeys. They inserted 25 human EPS cells into each of 132 monkey embryos and raised the chimeras in culture vessels for up to 20 days.
The team reports today in Cell that human cells showed maintenance power: after 13 days, they were still present in about a third of the chimeras. Human cells seemed to integrate with monkey cells and began to specialize in cell types that would grow in different organs.
By analyzing genetic activity, the researchers identified molecular pathways that were started or appeared in chimeras, possibly promoting integration between human and monkey cells. Izpisúa Belmonte says manipulating some of these pathways can help human cells survive in embryos of species “more suitable for regenerative medicine.”
However, human and monkey cells have not taken root, notes Andrew Crane, a UM stem cell biologist. Human cells often stick together, leading him to wonder if there is “another barrier we don’t see” that could prevent human cells from thriving if embryos should continue to grow.
In the United States, federal funding cannot be used to create certain types of chimeras, including early nonhuman primate embryos that contain human stem cells. The new study was conducted in China and funded by Chinese government sources, a Spanish university and an American foundation. Bioethicist Karen Maschke of the Hastings Center in New York says she is pleased that the work, which went through layers of institutional review and the advice of two independent bioethicists, was done responsibly.
Man-ape chimeras raise a concern, addressed in a report published last week by the National Academies of Science, Engineering and Medicine (p. 218): that human nerve cells could enter the animals’ brains and alter their mental abilities. But this concern is debatable for the chimeras in this study because they do not have a nervous system. They “cannot experience pain and are not conscious,” says bioethicist Katrien Devolder of Oxford University. “If ape-man chimeras were allowed to develop further,” she says, “it would be a very different story.”