Skin cells converted to brain cells without intermediate stem cell stage

By Dr. Ananya Mandal, MDFeb 2 2012

Researchers from California have successfully converted mouse skin cells into cells which develop into the main components of the brain. The experiment, reported in Proceedings of the National Academy of Sciences, is notable because it skipped the middle “stem cell” stage in the process.

The researchers said they were “thrilled” at the potential medical uses. They added that more studies and research was necessary before this could be replicated in humans.

Stem cells, which can become any other specialist type of cell from brain to bone, are thought to have huge promise in a range of treatments. Many trials are taking place, such as in stroke patients or specific forms of blindness. The main problem with this research is the source of the cells. There are ethical concerns around embryonic stem cells and patients would need to take immunosuppressant drugs as any stem cell tissue would not match their own.

An alternative method has been to take skin cells and reprogram them into “induced” stem cells. These could be made from a patient's own cells and then turned into the cell type required, however, the process results in cancer-causing genes being activated.

In this latest research the team at the Stanford University School of Medicine in California, found another option - converting a person's own skin cells into specialist cells, without creating “induced” stem cells. It has already transformed skin cells directly into neurons. While the cells can go on to become neurons, they can also differentiate into atrocytes and oligodendrocytes, which maintain neurons and connect them to one another in order to transmit signals. Neural precursor cells are also easily stored in large numbers and better for lab work, the researchers noted. This could be critical if the cells were to be used in any therapy.

Brain cells and skin cells contain the same genetic information, however, the genetic code is interpreted differently in each. This is controlled by “transcription factors” explained scientists. The scientists used a virus to infect skin cells with three transcription factors known to be at high levels in neural precursor cells. After three weeks about one in 10 of the cells became neural precursor cells. “Not only do these cells appear functional in the laboratory, they also seem to be able to integrate ... in an animal model,” said author and graduate student Ernesto Lujan in a Stanford news release.

Lead researcher Prof Marius Wernig said, “We are thrilled about the prospects for potential medical use of these cells. 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. More work needs to be done to generate similar cells from human skin cells and assess their safety and efficacy.” The Stanford team is working to replicate the work with skin cells from adult mice and humans.

Dr Deepak Srivastava, who has researched converting cells into heart muscle, said the study, “Opens the door to consider new ways to regenerate damaged neurons using cells surrounding the area of injury.”