"This is just a small step along the way, but it's an important one," says stem cell researcher Paul Lerou of Children's Hospital Boston and Boston's Brigham and Women's Hospital. Lerou and his colleagues extracted stem cells from embryolike clusters of cells grown from the unfertilized eggs of female mice that the researchers coaxed into dividing. They injected the stem cells back into related mice, where they grew without being rejected by immune cells, the group reports in a paper published online December 14 by Science.
In principle the method could make it easier to create human stem cells and potentially carry out still far-off treatments for spinal cord injuries and degenerative diseases such as Alzheimer's and Parkinson's. "I think it's very attractive and this paper shows it has the potential to do really great things," says molecular biologist Kent Vrana of Penn State University.
Researchers have previously proposed growing embryonic stem cells using so-called therapeutic cloning, in which the nucleus of a donor's body cell is placed in an egg cell stripped of its nucleus. The problem is that the process would likely require at least 100 donated egg cells to work even once, judging from the number of eggs needed to clone animals.
To avoid this, Lerou's team in essence tricked unfertilized egg cells from mice into dividing the same way that a growing embryo would. Researchers induce this effect, called parthenogenesis, by exposing ovulating or immature eggs to a chemical that prevents them from splitting their two sets of chromosomes into two daughter cells with one set each. The process works about 70 percent of the time in mice and nonhuman primates, Lerou says.
Normally, such cells would be genetically mismatched with cells like those of their donor. Specifically, the donor would have genes for two different proteins called major histocompatibility complexes (MHC), one on each chromosome 17 in its genome. The so-called parthenote embryo, however, would have identical pairs of chromosomes, so it would have only one MHC. If a cell's MHCs do not match those of the rest of the organism, the immune system will attack and reject those cells in much the same way it rejects a transplanted organ that comes from an incompatible donor.
A parthenote's chromosomes are not completely identical, however. An egg cell starts off containing both sets of chromosomes, each of which is copied and one of which then gets expelled. Before that expulsion, the different chromosomes mix together a bit so that a chromosome that would normally have one MHC protein sometimes gets the other one instead, giving the parthenote two different MHCs.
The researchers hypothesized that they could make compatible matches if they were able to isolate the few cells in the bunch with both MHCs. Toward that end, they analyzed the genomes of individual cells from their parthenotes and, lo and behold, found a few with both proteins. When they transplanted those cells into mice that also had a mixed set of MHC proteins, the parthenote cells took hold and grew into the three major kinds of embryonic tissue.
"It's pretty solid data," says stem cell researcher Jose Cibelli of Michigan State University. "If that is going to hold true in humans we don't know, but it is very encouraging." He cautions, however, that stem cells of any origin must still prove stable when transplanted to hold any hope of treating disease. One possible hitch: Parthenotes might not grow properly, because they lack important contributions from male genes.