When studying disease, scientists often rely on mice, which they can genetically manipulate to try to figure out the cause of illnesses. But mice are not always the best models for human cell behavior. One glaring example: mouse embryonic stem cells, first derived roughly 25 years ago. This is because mouse stem cells use different chemical pathways than their human counterparts do to retain their pluripotency (ability to morph into any tissue type). This difference has meant that mouse stem cells are a poor research proxy for human stem cells.
But researchers report this week in Nature that they discovered a new mouse embryo–derived stem cell that behaves much like a human embryonic stem cell—which could make mouse models more valuable research tools. The teams, from the universities of Cambridge and Oxford in England, say the key may be in the timing: They plucked the cells from mouse embryos two days later than researchers ordinarily do.
The scientists say these cells' humanlike quality can provide insight into how human embryonic cells operate.
"This is a new type of embryonic stem cell isolated from mice—in both studies—and [from] rats [in our research] that has very strikingly similar properties to human embryonic stem cells," says Roger Pederson, a professor of regenerative medicine at Cambridge and a co-author of one paper. "This is very intriguing, because it can provide a model for studying and accelerating studies of human embryonic stem cells."
Sir Richard Gardner, a professor of mammalian development at Oxford, adds that the findings indicate that researchers can derive pluripotent stem cells similar to those in humans from mice (and, conceivably, from a host of other mammals) if they harvest them at different stages of an embryo's development.
Both groups extracted cells during a phase in embryonic development when pluripotent cells are huddled in the epiblast (the innermost layer of the embryo). This stage of development occurs just before gastrulation, during which embryonic cells begin to mature into tissue that will ultimately become the lungs, heart, kidneys, blood and everything else in the human body. The Cambridge group also found and harvested cells in rats, which had previously failed to produce viable stem cells in the lab.
Pedersen says the new finding in combination with the wealth on information available on mouse genetics could help researchers learn more about human diseases, such as type 1 diabetes. "If you don't know where you are to start with, you're going to fumble around a lot and that's where we've been with regard to human embryonic stem cells," he says.
Gardner sees things differently. He believes the results of these studies demonstrate that the properties of human embryonic stem cells are likely conserved in other mammals in addition to the mouse. In fact, given that many disease models in mice are poor for studying human illness—including, he points out, cystic fibrosis and other pulmonary disorders, for which scientists rely on sheep—the new finding should encourage scientists to find mammals that can serve as better embryonic stem cell proxies for humans.
"What this tells us is if you use different conditions, you can get pluripotential stem cells out of the mouse, so it's going to encourage people to go back and do the same on any other mammal," he explains. "There is no reason why you shouldn't be able to find an animal that is more close to the human in this regard than the mouse."