- Scientists have created a human-mouse chimera with 4 percent human cells—the most of any chimera to date.
- While the embryos showed traces of human cells in most kinds of tissue, including the heart and liver, their germline tissue (which goes on to become sperm or eggs) contained none.
- Their work was published in the journal Science Advances.
Scientists at the University at Buffalo and the Roswell Park Cancer Institute have bred a new form of human-mouse chimera with the highest incidence of human cells ever recorded. Chimeras are organisms made up of a mixture of genetically different tissues—in this case, mouse cells and human stem cells. The team published its work in the journal Science Advances.
Two weeks after the researchers injected human stem cells into the developing mouse embryos, one of the newborn mice exhibited 4 percent human cells—a major advance, considering human and animal cells don’t typically jive well. While they’re still mostly just mice—and only a tad bit human—the breakthrough marks a step toward more advanced genetically modified embryos in the future.
“It has not been possible to generate naïve [human stem cells] that substantially contribute to mouse embryos,” the scientists say in the paper’s abstract. Their work “may enable applications such as human organ generation in animals.”
In the study, the scientists had to turn back the clock on human pluripotent stem cells to the naïve stage. To do that, they discovered they could briefly inhibit a protein in the stem cells for up to three hours, so they could hopefully reassemble into any type of tissue desired.
Next, the scientists infused these young stem cells into the mouse embryos and let them develop for just over two weeks. They found evidence of human cells in the developing liver, brain, eyes, heart, blood, and bone marrow. Once the team examined the embryos’ DNA, it turned out human cells accounted for anywhere between 0.1 and 4 percent of the developing tissues.
However, none of the developing germline tissue—which goes on to create eggs or sperm—contained traces of human cells. That’s somewhat reassuring, since chimeras with the ability to reproduce could become an ethical nightmare.
Braiding together human and mouse cells might seem bizarre, but there is precedent for such work in other animals, like pigs, cows, and sheep. One of the major early milestones in the field dates back to 1984, when scientists produced a chimeric sheep-goat by combining embryos from each animal. The creature survived through adulthood.
Last December, Chinese researchers created two monkey-pig chimeras after genetically modifying cynomolgus monkey cells in culture. Those animals lived for just a week, proving the process is still very unpredictable.
Chimeras, while certainly in a nascent stage of scientific exploration—and a controversial one, too, as detractors think of the work as “playing God”—hold significant promise. If animal cells can eventually fuse together with human cells in a high enough proportion, it’s possible we could one day see entire human organs grown in vivo. That could have potential to shorten those notoriously long waitlists for organ transplants.
Because this study represents the highest level of human cells in a chimera yet, it’s a momentous leap toward that version of medical reality. But it’s important to take these results with a grain of salt until more researchers can replicate the process.
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