Stanford researchers have discovered how to turn a mouse skin cell directly into a nerve cell — eliminating the need to go through a stem cell stage.
“The fact that we’re able to do this is extremely stunning,” said pathology Prof. Marius Wernig, the primary author of the paper.
Researchers in Wernig’s lab took skin cells from mice and, using three factors in the laboratory, transformed them directly into induced nerve cells. The nerve cells are capable of creating an action potential and creating synapses, along with other neural functions.
“This is proof of principle that [direct transformation] can happen,” said Irving Weismann MD ’65, a pathology professor and leading stem cell researcher at Stanford. “However, it still has to be done in humans.”
Before this breakthrough, in order to transform one type of cell into another, the original cell had to be induced back into a stem cell. Then the stem cell could differentiate into a number of different types of cells.
“[By] going backward, you can imagine it’s possible to induce, but this is a completely new way . . . a cell in the body never has to [directly transform],” Wernig said. “It’s very artificial, if you will.”
Though this process is extremely young and needs more exploration, it has many possible clinical applications, Weissman explained. For example, examining the cells in culture could lead to breakthroughs in many neurological diseases.
“[Someone could] take skin cells from someone who has a disease, reprogram them into neurons and see what’s gone wrong if they have Parkinson’s or Lou Gehrig’s disease,” he said.
Wernig expressed similar hopes for the new cells. “[We could] capture disease processes with these cells in these systems. They can’t be mimicked in animal cells really well . . . [We’re] intrigued to have the idea to get human neurons and study diseases in the dish.”
The only successful transformation thus far has been from a skin cell to a nerve cell, but this new discovery opens the door to transforming skin cells into any type of cell. Both Weismann and Wernig predict an onslaught of new experiments this year trying to achieve these different transformations.
But the discovery, however successful, does not entirely bypass the ethical and political issues surrounding the use of embryonic stem cells in research; it only avoids the process of induced pluripotent stem cell, or “iPS,” creation.
iPS are skin cells reprogrammed into stem cells that can then differentiate just like embryonic stem cells. iPS were originally considered a solution to the embryonic stem cell issue; however, this new discovery only shortcuts the iPS process, rather than providing any novel option to avoid the controversy of stem cell research.
But Wernig defended the research’s potential, saying that “even though they are stem cells, they are not from embryos . . . there are no ethical issues whatsoever.”
However, both Wernig and Weissman were quick to point out that this new technique is in its infancy and needs much more research to truly take hold as an accepted technique.
“These are very, very early times both for iPS and for our new technology,” Wernig said. “We clearly have to explore both better to determine the best technology.”
Weissman also pointed out that this new technique will not eliminate the need for other means of studying stem cells, including embryonic stem cell research.
“[The direct transformation technique] does not replace reprogramming to embryonic stem cells,” he said.
The results were published in Nature on Saturday.