For the first time, they have managed to regenerate damaged areas of the cerebral cortex of living animals by transforming a type of support cell found in the brain.
The cerebral cortex, which is the outer layer of tissue in the brain, is involved in controlling movement, interpreting the senses, conscious thought and memory. Usually almost no new neurons are grown in this area of the brain in adults, so once the cells are damaged or die, they are not replaced.
However, by injecting mice with viruses carrying a short piece of extra genetic code, scientists were able to coax structural cells, called NG2 glia, in the damaged part of the brain to develop into neurons. These then grew in the injured area and were found to be capable of receiving signals from neurons around the damaged area.
The study raises hopes that damaged brain tissue can be repaired in patients who suffer from epilepsy, or those who have had a stroke or a traumatic injury.
Scientists have previously used stem cells grown in the laboratory, which were then injected into patients, to help repair damage caused by stroke.
However, the latest research, which is published in the journal Stem Cell Reports, raises the prospect of repairing injuries using cells that are already in the patient’s head, reducing the risk of rejection and other complications.
The researchers cautioned, however, that it could take up to two decades before such therapies are ready to be used in human patients.
Dr Benedikt Berninger, a geneticist at the Ludwig-Maximillians University in Munich who was one of the lead researchers, said: “A lot of basic research is required until the field can move to clinics.”
“In the cortex we can think of Alzheimer’s disease and stroke, but these diseases involve massive tissue degeneration, so it will be difficult. Other diseases like epilepsy may be more amenable,” he added. “Regenerating neurons that relay sensory or motor responses is certainly more likely to work than regenerating memory circuits.”
Creating new neurons will not restore memories that were coded in the connections between degenerating cells, he said, but it may at least allow the system to acquire new memories.
The scientists genetically modified retroviruses to carry genes for the transcription factor Sox2, which is known to play an important role in the development of stem cells. The team injected the viruses into the damaged brains of mice, where they incorporated the genetic information into cells.
This transformed adult NG2 glia cells (which normally help maintain the physical structure of the brain and supply it with nutrients) into neurons. The new neurons only grew in the injured areas and did not grow in the brains of uninjured mice.
By measuring the electrical conductance of the new cells, the scientists were able to confirm that the new neurons had been incorporated into the brain’s neural networks and could receive signals.
Prof Magdalena Götz, a neuroscientist at Ludwig-Maximilians University Munich who was involved in the research, said that they hoped to develop drugs to promote the transformation of the cells rather than using viruses.
“We have to cope with the neurons we are born with for the rest of our life in most brain regions. Once we lose a certain number, there is presently nothing one can do to make new neurons,” she said. “Therefore it is so important to study how cells in the brain could be inspired to generate new neurons when needed.”
Professor Anthony Hollander, head of the Institute of Integrative Biology at the University of Liverpool, described the latest work as encouraging. “The most interesting observation here is that injured brain tissue appears to be a better environment for this to happen than normal brain tissue, which is obviously a good thing if the aim ultimately is to treat injured tissue,” he said.
“It is far too early to say if this observation will be of clinical relevance – for example the nature of injury could be critical and the time after injury could be equally important.”