Closer to repairing the brain with its own stem cells

Hobart researcher Kaylene Young believes she can persuade lazy stem cells in our brain to repair brain injuries and even treat diseases such as multiple sclerosis and Alzheimer’s.

Dr Kaylene Young of the Menzies Research Institute Tasmania has received an inaugural $50,000 Metcalf Prize from the National Stem Cell Foundation of Australia in recognition of her leadership in stem cell research.

She and her colleagues have found neural stem cells and oligodendrocyte progenitor cells (OPCs)—which feed, protect and assist nerve cells—in the outer part of the brain most prone to damage, known as the cortex.

By understanding the behaviour and function of these cells, they one day hope to use them for treating nervous and brain disorders or damage.

“Our ultimate goal is to harness the regenerative capacity of these cells for the treatment of neurodegenerative diseases, mental health disorders, and traumatic brain injury,” says Kaylene.

To assist in her work, the National Stem Cell Foundation of Australia has awarded Dr Kaylene Young—National Health and Medical Research Council RD Wright Biomedical Research Fellow and Research Group Leader at the University of Tasmania—one of two inaugural Donald Metcalf prizes each worth $50,000.

The awards are named for Professor Donald Metcalf, AC, who transformed cancer treatment with his discoveries of critical molecules that tell stem cells to multiply and mature to boost the immune system.

The progenitor cells are the only cells, apart from other neurons, with which nerve cells communicate electrically, Kaylene says, and that means there may be an electrical means of controlling them or modifying their behaviour to induce regeneration.

“This electrical signalling system has the potential to be activated by a non-invasive stimulus, allowing us to promote their activity and increase their generation as a potential treatment for multiple sclerosis, a disease that induces considerable oligodendrocyte loss.

“We have recently discovered that adult-born oligodendrocytes continually remodel neuronal insulation in the normal central nervous system. This represents a fundamental shift in our understanding of how plastic and malleable our nervous system is,” says Kaylene.

“We’ve created the Metcalf Prizes to encourage early-career stem cell research pioneers,” says Dr Graeme Blackman,OAM, the Chairman of the Foundation. “We were stunned by the quality of the applications. Our inaugural winners, Kaylene Young and Jose Polo, stood out from a remarkable field of young research leaders. We can expect great things from Australian stem cell research in next few years.”

It used to be thought that by the time you reached adulthood you had all the brain cells you were ever going to generate. After that, it was said, any brain cells you lost or injured could never be replaced—and that made brain damage particularly hard to treat. Then, a little over 20 years ago, stem cells were found to be actively dividing in at least two parts of the brain—the hippocampus, where memories are formed, and the olfactory bulb.

Now, Dr Kaylene Young of the Menzies Research Institute Tasmania is talking of treatments for brain injury and diseases such as multiple sclerosis and Alzheimer’s using such neural stem cells and also the cells which feed, protect and assist neurons, known as oligodendrocytes. She and her colleagues have found, and are studying neural stem cells and oligodendrocyte progenitor cells (OPCs) in the cortex, the outer part of the brain most prone to damage.

Kaylene and her group want to understand the behaviour and function of neural stem cells and OPCs with the aim of using them for treatment of nervous and brain disorders or damage, particularly in the cortex.

In terms of stem cells for the cortex, one strategy could be to find some means of enticing them to migrate from the hippocampus or the olfactory bulb. But Kaylene and her colleagues at Monash University and the University of Melbourne have found stem cells naturally occurring in the cortex itself. “They are quiescent, however, just plain lazy. Their capacity to divide and grow is not turned on. But when we take them out into culture, we can make new nerve cells from them.” So one aim of her work is to determine how these cells can be triggered to do the same in the cortex.

“Our experiments will determine whether they can be activated in the brain, and respond by generating a large number of new, functional neurons following an injury. We also aim to determine whether these neurons can survive long term within the brain, and contribute to sustained repair.”

The OPCs are quite a different story. The cells they generate, oligodendrocytes, are found in association with nerve cells all over the body. They perform several roles, including providing sugar and nutrients to neurons, and fashioning the fatty, myelin sheath which both protects neurons and speeds up their transmission. Once the brain lays down electrical wiring, myelin paves the way, forming the original information superhighway. Both multiple sclerosis and Alzheimer’s disease cause problems when they interrupt nervous transmission by interfering with the myelin sheath.

In a sense, Kaylene has been the right person in the right place at the right time. After winning a scholarship to do a science degree at Monash University, it didn’t take her long to decide that the area that interested her most was how the internal systems of animals fitted together and functioned, the field known as physiology. And of that, what excited her was neuroscience, the study of the nervous system and the brain.

It was the right time because she began her undergraduate degree in the mid-90s, just a few years after the discovery of neural stem cells made brain and nervous system repair seem far more possible. And it was the right place, because one of the world leaders in neural stem cell research, Professor Perry Bartlett, was working in Melbourne at the Walter and Eliza Hall Institute. After carefully quizzing her about her studies and interests, he agreed to take her on as a PhD student.

When she gained her doctorate in 2005, she moved to the UK as a postdoctoral fellow at University College, London. She came back to Australia in 2011 to set up her own research group at the Menzies Research Institute Tasmania.

Kaylene wants to use the Metcalf Prize money to further her work in several ways. There are obvious direct benefits, such as purchasing necessary new equipment for her laboratory and allowing her to attend conferences to keep in touch and swap ideas with other leading researchers in her field. But also on her list is specialist training for her graduate students. One thing she has in mind is a retreat to provide members of her laboratory with skills for writing up and communicating research.

“Being able to communicate science, both to the public and also to other scientists, is really what allows us to spread information. We are always building on each other’s work. And if we aren’t able to communicate in a clear way, then messages get missed.”

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