Brain cells made from human skin

The Independent reports today that there is “hope for millions of Alzheimer’s sufferers as scientists make brain cells from human skin”. It said that “scientists had managed to convert a person's skin tissue into functioning nerve cells – bypassing an intermediate stem-cell stage – by the relatively simple procedure of adding a few short strands of RNA, a genetic molecule similar to DNA”.

This is an interesting study which builds on previous research in this area. It may enable scientists to study the behaviour of neurons (brain cells) more easily in the future. Eventually, this might lead to the development and testing of treatments for brain diseases in the laboratory.

However, this research is still in the early stages. Any application to the prevention or treatment of brain disease such as Alzheimer’s in humans is unclear. Whether converted neurons grown in the laboratory can ever be used to replace diseased or abnormal cells in living human brains will need considerably more research.

Where did the story come from?

The study was carried out by researchers from Stanford University, California. Funding was provided by the Howard Hughes Medical Institute and the National Institutes of Health. The study was published in the (peer-reviewed) journal Nature .

The Independent reported the study accurately, although its headline claiming that the study brings hope to “millions of Alzheimer’s sufferers” could be misleading. Although this is exciting work, any application to the prevention or treatment of brain disease in humans is still uncertain.

What kind of research was this?

This was an experimental laboratory study, which used genetic technology to see if human skin cells (called fibroblasts) could be converted into neurons (brain cells). At present, scientists find it hard to study neurons in the laboratory because, unlike skin or blood cells for example, it would clearly be unethical to take them from a living human.

Previously, they had found that stem cells converted from skin cells could be transformed into neurons, but the new study aimed to find out if skin cells could be converted directly into neurons. Earlier this year, other scientists reported that they had managed to convert skin cells directly into neurons by adding to them a combination of four neurogenic transcription factors. Transcription factors are proteins that bind to specific DNA sequences, controlling the flow of genetic information and cell processes. In this latest experiment, scientists adopted a different technique, using genetic material called microRNA.

What did the research involve?

In a series of experiments, the researchers used both skin cells from neonatal foreskin and also adult skin cells. To the cells they added two short chains of genetic material, known as microRNA (RNA is a molecule similar to DNA, essential to all forms of life). The particular RNA molecules that they used had previously been found to be important in triggering neural stem cells into becoming mature neurons.

In this study, they used a virus to carry the microRNA into skin cells. The resulting cells were then tested for neuronal activity. To do this, the researchers examined the skin fibroblasts under the microscope to see how many of the cells had developed the ability to transport calcium into the cells.

This ability is specific to neurons and shows that the cells had taken on the characteristics of neurons, such as their ability to transmit electrical nerve signals. They also looked at whether the cells contained neurotransmitters, like neurons do.

As a further experiment they added two transcription factors to the microRNA-treated cells used in the earlier study to see if these sped up the conversion of skin cells into neurons. They did this to test whether it was the transcription factor or the microRNA that was having the effect.

What were the basic results?

The researchers found that up to 2-3 % of the skin cells converted to neurons. The cells generated the electrical signals that neurons use to communicate with each other. They also started to grow the cell structures (synaptic vesicles) that are needed to store neurotransmitters, the chemical used for passing messages between brain cells.

The researchers say that the neurons were characteristic of those found in the frontal cortex, the part of the brain involved in thinking and reasoning. Some of them resembled “inhibitory” neurons, cells whose role is to control the activity of other neurons.

When they added two of the transcription factors that had been used in the earlier experiment, the number of skin cells converted into neurons rose to 20 per cent.

How did the researchers interpret the results?

The researchers say that being able to generate neurons from easily accessible cells, such as skin cells, would make it easier to study neuronal development, particularly in neurological diseases. They also suggest that different types of brain cells might be made from skin cells by using different techniques with the microRNA.

Conclusion

This work raises the possibility that neurons might be grown directly from more easily accessible cells and could, in future, enable scientists to study these type of cells more easily. This could lead to an increased understanding of the abnormalities involved in various neurological diseases such as Alzheimer’s. However, there is a long way to go before we know how far this research can contribute to preventing or treating such diseases.