Mice are bred all the time in laboratories around the world. So, generally speaking, the birth of a couple dozen more lab mice isn’t worth noting.
But this week, two groups of scientists in China separately reported that they had created a new kind of mouse — grown entirely from a type of stem cell that originated from already mature cells, instead of from embryos. Researchers took skin cells from donor mice, reprogrammed them to revert back to an embryonic state, then programmed them again to develop into an entire mouse pup.
This feat has been achieved before using embryonic stem cells, but never using the new type of stem cells known as induced pluripotent stem cells, or iPS cells, which are typically derived from skin cells. Since iPS cells were first discovered in 2006, many groups have tried, unsuccessfully, to generate whole animals from them. Researchers feared the failures indicated that iPS cells were simply not as versatile as embryonic stem cells. “It has been a lingering concern, why these cells couldn’t make … animals,” says Dr. Robert Blelloch, a stem-cell scientist at the University of California, San Francisco.
Now the two studies, one led by Qi Zhou and Fanyi Zeng of the Chinese Academy of Sciences and Shanghai Jiao Tong University and the other by Shaorong Gao at the National Institute of Biological Sciences, offer strong evidence to the contrary. The fact that iPS cells can give rise to an entirely new mouse, and one that can sire offspring, as one of the studies showed, suggests that the cells are as versatile as those from embryos, and may prove useful in generating other kinds of functioning cells that can safely treat patients with conditions such as Parkinson’s, diabetes and heart disease — or even prevent these diseases altogether. “It’s further evidence that these are not some bizarre cells out there, and that they are very much like normal embryonic stem cells,” says Blelloch.
That’s welcome news for stem-cell experts — as well as patients and doctors around the world — who hope that stem cells will yield new treatments for disease. Furthermore, iPS cells can be derived from any tissue in the adult, while embryonic stem cells require the destruction of an embryo — an enduringly controversial factor that has stymied embryonic-stem-cell science in the U.S.
But the studies’ success again raises the specter of cloning: Could humans be reproduced using far-more-accessible tissues, such as skin, as opposed to embryos While theoretically possible, both research teams stress that the purpose of their research is not to find an efficient way to clone people, but to expose some of the basic mechanisms behind development. “We are using the mouse iPS cells to find out [the answers] to some basic science questions,” said Zeng, a professor at Shanghai Jiao Tong University and a co-author on the paper that appears in the journal Nature, in a telephone briefing with reporters.
Those answers may still be a few years away. Zeng said that some of the 27 mice born from iPS cells were not completely normal, and while she did not provide further details, she said she and her group are currently studying why. Other mice born using the procedure, however, were able to mate with traditionally bred mice to generate more than 200 second-generation offspring, which went on to sire more than 100 third-generation pups. “So far we haven’t detected much tumor [growth] on a big, global scale,” Zeng told reporters. “But we still have a lot to do, and a lot of animals [to study] so we are currently working on looking at the abnormalities in these offspring.”
To obtain live mice, both groups took iPS cells and injected them into two-cell mouse blastocysts, which are early-stage embryos that have double the normal number of chromosomes, rendering them unable to develop into a fully formed animal. Such blastocysts can form only tissues, such as the placenta. So by injecting iPS cells into this two-celled vesicle for incubation, scientists could be sure that any resulting embryo — or animal — derived entirely from the stem cells.
That’s exactly what the two groups independently showed. Gao, whose paper appears in Cell Stem Cell, was able to generate one mouse from 400 blastocysts. Zeng’s team had better success, birthing 22 pups from 1,500 injected blastocysts. But the process remains inefficient, and both groups are working to find ways to increase its stability and consistency. Generating iPS cells is hit or miss to begin with — while skin cells are a plentiful starting material, they are obstinate. They must be forced to revert back to an embryonic state by the introduction of four genes that erase the skin cell’s genetic memory; only about .01% to 0.1% of skin cells respond. And an even smaller percentage of those cells are biologically plastic enough to give rise to an entirely new animal. One trick Zeng’s team used was to select iPS cells that are still young enough to retain their ability to morph into all of the tissues in an adult mouse. Her group compared iPS cells that were 14, 20 and 36 days old; they saw the most live pups born when they injected 14-day-old iPS cells into the blastocysts.
Still, says Blelloch, it’s not clear exactly why some cells successfully produce a live pup, while others do not. “What is different about these cells We don’t know yet,” he says.
Although the details of the experiments’ success are not yet understood, the findings give scientists more confidence in the power of iPS cells. Among Zeng’s mice, the oldest has now survived for nine months, and Gao’s iPS mouse is two months old. Both teams conducted genetic analyses of the cells in the iPS-generated mice and found that their genes were similar to those from mice grown from embryonic stem cells. While additional studies need to be done to determine whether iPS cells are functionally equivalent to embryonic stem cells — the gold standard — stem-cell scientists say the results reported by the Chinese groups are encouraging.
See TIME’s cover story “Stem Cells: The Hope and the Hype.” See the top 10 scientific discoveries of 2008.
