Bypassing the stem cell stage, researchers at the Stanford University School of Medicine in California converted mouse skin cells directly into neural precursor cells, the cells that go on to form the three main types of cell in the brain and nervous system. They write about their findings in the 30 January early online issue of the Proceedings of the National Academy of Sciences.
The findings of this and an earlier study question the idea that pluripotency (the ability to become virtually any other cell in the body, a key characteristic of stem cells) is a necessary stage in the conversion of one cell type to another. In the earlier study, the same team transformed mouse and human skin cells directly into functional neurons. But this study is a substantial advance on the earlier one for two reasons.
First, neural precursor cells can not only differentiate into neurons, they can also become either of the two other main types of cell in the nervous system: astrocytes and oligodendrocytes. Astrocytes are star-shaped glia cells that hold neurons in place, get nutrients to them, and digest parts of dead neurons. Oligodendrocytes make the myelin that insulates nerve fibers that connect neurons to one another and allows them to transmit signals.
And secondly, neural precursor cells are a more useful and versatile end-product for the lab, where they can be cultivated in large numbers for transplantation or drug screening. Together, the two studies raise the possibility that embryonic stem cell research and induced pluripotency could be replaced by a more direct way of making specific cell types for treatments and research.
The problem with embryonic stem cells, although they are considered the "gold standard" in generating new types of cell, is the ethical question of where they come from, and also because they don't come from the patient's own body, the patient has to take drugs to stop their immune system rejecting the new tissue.
Induced pluripotency, where the patient's own cells are reprogrammed into stem cells, appears to overcome the ethical and immune rejection problems of embryonic stem cells, except they introduce the risk of switching on genes that cause cancer. Although this risk can be reduced by screening out unwanted pluripotent cells, it introduces a cost.
The senior author of the new study is Dr Marius Wernig, assistant professor of pathology and a member of Stanford's Institute for Stem Cell Biology and Regenerative Medicine. He told the press he and his colleagues were "thrilled" about the medical potential of their findings.
"We've shown the cells can integrate into a mouse brain and produce a missing protein important for the conduction of electrical signal by the neurons. This is important because the mouse model we used mimics that of a human genetic brain disease," said Wernig.
However, he cautioned that more work is needed before they can show a similar conversion from human skin cells is not only possible and effective, but also safe.
For the study, Wernig and colleages infected embryonic mouse skin cells (a cell line commonly used in labs) with a virus carrying three transcription factors (Brn2, Sox2 and FoxG1) known to be present at a high level in neural precursor cells. In just over three weeks, one in ten of the skin cells had started to look and act like neural precursor cells. In the lab, they confirmed the transformed cells were expressing the appropriate genes and had the same shape and function as naturally derived neural precursor cells.
And to confirm them in animals, they injected the new cells into the brains of newborn mice bred to lack to ability to make the myelin sheath that surrounds nerve fibers. After ten weeks, the new cells had differentiated into oligodendroytes and had begun to coat the mice's nerve fibers with myelin. The team is now hoping to repeat their success with skin cells from adult mice and humans.
Funds from the California Institute for Regenerative Medicine, the New York Stem Cell Foundation, the Ellison Medical Foundation, the Stinehart-Reed Foundation and the National Institutes of Health helped pay for the study.
