For the first time, scientists have created primates whose cells carry one of several sets of genetic instructions instead of one consistent assemblage of DNA. The three rhesus monkeys are chimeras, conglomerates of cells from up to six genetically different embryos.
Creating the monkey chimeras was much harder than achieving a similar result in mice, suggesting that embryonic stem cells from primates, probably including humans, are less flexible than their mouse counterparts. Those findings could have implications for regenerative medicine, which seeks to create replacement organs and cells from stem cells — efforts often first tested in mice.
Some people have worried that scientists working with embryonic stem cells, which have the potential to develop into any type of cell in the body, might inadvertently grow a human fetus in the lab. The new work shows that’s probably not going to happen, says developmental biologist Gerald Schatten of the University of Pittsburgh School of Medicine. It also means stem cells are less likely to run wild, creating tumors or growing into the wrong type of cell once implanted in a patient.
“It’s almost like nature’s safety cap,” he says.
Researchers working with stem cells from mice and other animals use the creation of chimeras as the gold standard for showing that isolated embryonic stem cells really do have the power to generate any of the body’s many cell types. Since no one had ever made a chimeric primate before, the evidence that human and monkey cells are able to blossom into any type of cell has been mostly circumstantial.
“So far we just assume they are,” says developmental and stem cell biologist Shoukhrat Mitalipov of the Oregon Health & Science University in Beaverton who led the new study, which appears online January 5 in Cell. But he and his crew put rhesus monkey cells to the test to see how much potential embryonic stem cells from primates really have.
The scientists added embryonic stem cells engineered to carry a glowing protein to an early-stage embryo called a blastocyst. The blastocyst is a ball of cells; the outer part becomes the placenta and other supporting tissues, while embryonic stem cells inside give rise to the actual fetus.
In mice, when embryonic stem cells are injected into a blastocyst, the resulting animal is a chimera containing cells from both the original blastocyst and the injected cells. In the new experiments, the researchers found that neither embryonic stem cells that had been grown in the lab nor freshly harvested ones could incorporate themselves into a developing primate fetus. The results “may show that what we have now is not as potent as we think,” Mitalipov says.
To create the chimeric animals, the researchers had to take a step backward from the blastocyst stage to embryos at the four-cell stage of development. The researchers created the chimeric monkeys by fusing together up to six of those four-cell-stage embryos. The three monkeys, named Chimero, Roku (Japanese for six) and Hex (Greek for six), are all normal and healthy, the researchers report.
Because rhesus monkey stem cells behave so much like human embryonic stem cells, researchers think the findings can be extrapolated to human cells. “But it’s possible this is going to be rhesus monkey–specific,” Mitalipov says. To find out, he hopes to make other chimeric primates, possibly starting with marmosets.