Laboratory-grown embryos mix human and apple cells for the first time | Science

By Mitch Leslie15 April 2021, 11:00

By letting human stem cells slide into the embryos of other animals, we can one day grow new organs for people with shaky hearts or kidneys. In a step towards the goal, researchers created the first embryos with a mixture of human and apse cells. These chimeras can help scientists create techniques for the cultivation of human tissue in species that are better suited for transplants, such as pigs.

“The paper is a beacon in the stem cell and germ fields that replace species,” says stem cell biologist Alejandro De Los Angeles of Yale University. The findings suggest mechanisms by which cells of one species can adapt to survive in the embryo of another, he adds. Daniel Garry, a stem cell biologist at the University of Minnesota (UM), Twin Cities.

In 2017, researchers reported that growing pancreas from mouse stem cells was inserted into rat embryos. The transplantation of organs into mice with diabetes eliminated the disease. But cells of more related species, such as pigs and humans, also did not survive. In the same year, developmental biologist Juan Carlos Izpisúa Belmonte of the Salk Institute for Biological Studies and colleagues reported that human stem cells had been injected into pig embryos. After developing embryos for 3 to 4 weeks in surrogate mother pigs, only one in every 100,000 of their cells was human.

The pig study used human skin cells reprogrammed into stem cells. But so-called extended pluripotent stem cells (EPS), made by exposing stem cells to a certain molecular cocktail, can yield a greater variety of tissues. In the new study, Izpisúa Belmonte, reproductive biologist Weizhi Ji from Kunming University of Science and Technology, and colleagues tested the more capable cells in a closer human family member – cynomolgus monkeys. They placed 25 human EPS cells in each of 132 monkey embryos and reared the chimera in up to 20 days in culture dishes.

The team reports today in Cell that the human cells showed endurance: After 13 days, they were still present in about one-third of the chimeras. It seems that the human cells integrate with the monkey cells and began to specialize in cell types that would develop in different organs.

By analyzing gene activity, the researchers identified molecular pathways that are turned on or off in the chimera, possibly promoting the integration between human and apse cells. Izpisúa Belmonte says that manipulating some of these pathways can help human cells survive in species embryos “that are more suitable for regenerative medicine.”

However, UM stem cell biologist Andrew Crane has still not completely merged. The human cells often get stuck together, making him wonder if there is another “barrier we do not see” that can prevent human cells from thriving as the embryos develop further.

In the United States, federal funding cannot be used to create certain types of chimeras, including early non-human primate embryos that contain human stem cells. The new study was conducted in China and funded by Chinese government sources, a Spanish university and a US foundation. Bioethicist Karen Maschke of the Hastings Center in New York says she is pleased that the work, which has surpassed low institutional oversight and received advice from two independent bioethicists, has been carried out responsibly.

Human-ape chimeras do cause concern, addressed in a report released last week by the National Academies of Sciences, Engineering, and Medicine (p. 218): that human nerve cells can penetrate animals’ brains and their mental abilities alter. But the concern is a big problem for the chimeras in this study because they do not have a nervous system. They “can experience no pain and are not conscious”, says bioethicist Katrien Devolder of the University of Oxford. “If the chimeras of apes were allowed to develop further,” she says, “it would be a very different story.”