In a study released this week in Science Advances, scientists report that they have engineered a mouse that’s a bit human.
Scientists at the University of Buffalo have shown that it’s possible to create mouse embryos that express very high levels of human cells. In one of the mouse embryos, 4% of the cells were actually human.
Those cells were present all over the nascent tissues in the mouse embryos, from retinal cells to red blood cells and liver cells.
That level of integration is “quite striking to me,” says Juan Carlos Izpisua Belmonte, a stem cell and developmental biologist at the Salk Institute for Biological Studies in La Jolla, Calif. If other scientists can replicate the findings, “it potentially represents a major advance,” says Izpisua Belmonte, who was not involved in the study.
Such chimeras could help reveal how a single cell can give rise to an entire organism. More humanized animals could also prove valuable in studying diseases such as malaria that affect people more than other animals. And with more advances, chimeras could ultimately turn out to be a source of human organs.
The new method’s success comes down to timing, says neuroscientist and stem cell biologist Jian Feng. To grow and thrive in a mouse embryo, human stem cells’ developmental clocks must be turned back to an earlier phase called the naïve stage. “You need to basically push the human cells back” to that phase, says Feng, of the University at Buffalo in New York.
Feng and his colleagues reset the stem cells’ clocks by silencing a protein called mTOR for three hours. This brief treatment shocked the cells back to their naïve stage, presumably restoring their ability to turn into any cell in the body.
Researchers injected batches of 10 to 12 of these more youthful human stem cells into mouse embryos containing about 60 to 80 mouse cells, and allowed the embryos to develop for 17 days.
To outward appearances, these embryos grew normally despite harboring human cells. By tallying DNA that was specific to either mouse or human, the researchers found that human cells accounted for between 0.1 and 4 percent of the total cells in the embryos.