Scientists Made Mouse Embryo with 4% Human Cells

The hybrid is what scientists call a human-animal chimera, a single organism that's made up of two different sets of cells -- in this case, a mouse embryo that has both mouse cells and human cells, CNN reported.

This human-mouse chimera has by far the highest number of human cells ever recorded in an animal, according to researchers. Their experiment suggests that many types of human cells can be generated in mouse embryos, and at a much faster rate than in human embryos.

And that, the scientists say, carries enormous potential for the treatment of human diseases, possibly even Covid-19.

Researchers from the State University of New York at Buffalo and the Roswell Park Comprehensive Cancer Center published the findings last week in the journal Science Advances.

These findings are important for a number of reasons, said Jian Feng, one of the study's authors and a professor of physiology and biophysics at the University at Buffalo.

For one, it shows that it's possible to generate many types of mature human cells in mouse embryos, which could potentially be used to make cells, tissues or organs to treat diseases.

In this study, the team of researchers injected 10 to 12 human stem cells into developing mouse embryos. Within 17 days, those stem cells developed into millions of mature cells, including human red blood cells and eye cells.

This figure shows a large quantity of human cells in a 17-day old mouse embryo. Most of the human cells are red blood cells, which are accumulated in the mouse fetal liver.

In a human embryo, it would take about eight weeks to generate human red blood cells and even longer to generate human eye cells, Feng said.

"These observations suggest that the mechanism that specify time in development can be changed," he wrote in an email to CNN. "With this implication, there will be more dramatic discoveries down the road."

In previous such research, scientists had only detected around 0.1% of human cells in mouse embryos.

That's why it's so striking that these human-mouse chimeras exhibited 4% human cells. And because of the technique that the team used to count the cells, Feng said even that figure is an underestimate.

The team achieved this feat by converting human pluripotent stem cells, which can potentially produce any cell or tissue the body needs to repair itself, into an earlier state.

Converting those cells made them compatible with the inner group of cells inside an early stage mouse embryo, which generates all the cells in the body. So when those earlier stage human cells were injected into mouse embryos, they developed much better than they otherwise would have.

"We reasoned that if we can make the human pluripotent stem cells behave like the mouse pluripotent stem cells, the human cells should mingle well with the mouse stem cells in a mouse blastocyst," Feng wrote. "And that is exactly we found."

The team's experiment indicates that the "the genetic program embodied in a mouse embryo and the genetic program embodied in human stem cells can crosstalk pretty well," Feng said.

In other words, there's enough evolutionary compatibility between mice and humans that mouse embryos are a relatively good environment for cultivating human cells.

"Life is a DNA-based software system that harnesses energy to produce information," Feng wrote. "This experiment is kind of like emulating Windows in a Mac."

Human-animal chimeras have been a point of ethical debate among scientists. Though they could be used to grow human organs for transplants, some scientists say there are serious risks that need to be explored.

"The possibilities have many researchers giddy with excitement. But they also raise serious ethical dilemmas about the moral status of these part-human animals," neuroscientist and animal advocate Lori Marino wrote in a 2017 op-ed for Stat News.

"Chimera test subjects must be human enough to serve as effective models for health research, but not so human that they qualify for protection from this research altogether."

Feng said their research is still in its early stages and more studies need to be conducted. But he added that the technology of making human stem cells more compatible with mouse embryos has a number of potential applications.

One, Feng said, is that it can generate better mouse models to study human diseases, including Covid-19. Mice can also be used to grow human immune cells or respiratory cells.

"Such chimeric mice would be very useful for studying Covid-19, which gravely impacts human, but barely affects mice," Feng said.

"Another example could be malaria, in which the pathogen specifically infect human red blood cells through a mosquito bite. If we can make a mouse with even more human red blood cells, it would be a very good model to study malaria."

Future studies could also explore whether this technique could be applied to larger animals, such as pigs, to generate organs for transplants, Feng said. Though he said such possibilities are far off, they hold promise.

"At the time of the first airplane, all the potential applications existed only in the minds of a few people," Feng said. "If the society were to decide that it was a horrible idea for humans to fly, we would miss a lot of things that turn out to be wonderful for everyone. A society that sees the world as what it is, not what it should be, is an effective society that can move forward."