Scientists create human brain cells

The news that Edinburgh scientists had created the world's first cloned mammal, Dolly the sheep, at the university's Roslin Institute made headlines around the world 16 years ago. Her birth raised hopes of the creation of a new generation of medicines, with a host of these breakthroughs occurring at the university's laboratories in the following decade. In a series of remarkable experiments, scientists at Edinburgh's Centre for Regenerative Medicine have created brain tissue from patients suffering from schizophrenia, bipolar depression and other mental illnesses. The work offers great rewards for doctors. From a scrap of skin taken from a patient, they can make neurones genetically identical to those in that person's brain. These brain cells, grown in the laboratory, can then be studied to reveal the neurological secrets of their condition. "A patient's neurones can tell us a great deal about the psychological conditions that affect them but you cannot stick a needle in someone's brain and take out its cells," said Professor Charles ffrench-Constant, the centre's director. "However, we have found a way round that. We can take a skin sample, make stem cells from it and then direct these stem cells to grow into brain cells. Essentially, we are turning a person's skin cells into brain. And we could do that in the future for the liver, the heart and other organs on which it is very difficult to carry out biopsies." The scientists are concentrating on a range of neurological conditions, including multiple sclerosis, Parkinson's disease and motor neurone disease. In addition, work is being carried out on schizophrenia and bipolar depression, two debilitating ailments that are triggered by malfunctions in brain activity. This latter project is directed by Royal Edinburgh Hospital's Professor Andrew McIntosh, who is working in collaboration with the Centre for Regenerative Medicine. "We are making different types of brain cells out of skin samples from people with schizophrenia and bipolar depression," he said. "Once we have assembled these, we look at standard psychological medicines, such as lithium, to see how they affect these cells in the laboratory. After that, we can start to screen new medicines. Our lines of brain cells would become testing platforms for new drugs. We should be able to start that work in a couple of years." In the past, scientists have studied brain tissue from people with conditions such as schizophrenia, but could only do so once an autopsy had been carried out. "It is difficult to get primary tissue to study until after a patient has died," added McIntosh. "Even then, that tissue is affected by whatever killed them and by the impact of the medication they had been taking for their condition, possibly for several decades." In addition, ffrench-Constant is planning experiments to create brain cells from patients suffering from multiple sclerosis, a disease that occurs when a person's immune system turns on his or her own nerve cells and starts destroying the myelin sheaths that protect the fibres that the nerve cells use to communicate with each other. The condition induces severe debilitation in many cases. "The problem with MS is that we cannot predict how patients will progress," said ffrench-Constant. The brain cells that make myelin and wrap it around the fibres of nerve cells are known as oligodendrocytes. "We will take skin samples from MS patients whose condition has progressed quickly and others in whom it is not changing much. Then we will make oligodendrocytes from those samples and see if there is an intrinsic difference between the two sets of patients. In other words, we will see if there is an underlying difference in people's myelin-making cells that explains, when they get MS, why some manage to repair the damage and others do not," said ffrench-Constant. Once the mechanism is revealed, the route to developing a new generation of MS drugs could be opened up, he added. "It is an attractive hypothesis. Stem cells will be the means of proving it." That is why the stem cell revolution is so important, said ffrench-Constant. "It has so much to offer in areas such as making models of diseases which should then allow you, hopefully, to develop all sorts of new treatments for a condition."