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      The ear as a model of nervous system repair

      Matthew Holley is Professor of Sensory Physiology at the University of Sheffield, and until recently was one of our trustees. He tells us about new research investigating how to repair nerve damage in the ear and how this could also have wider benefits in treating other central nervous system disorders.

      By: Tracey Pollard | 10 July 2015

      Hearing research is not always just about the ear. Investment in hearing research can also have a much wider impact, as shown by recent results from a collaboration between the Universities of Sheffield (UK) and Kyoto (Japan). Cell transplantation, where donor cells, such as stem cells, are transferred into the body in order to correct a problem caused by disease, can be used to replace lost auditory nerve cells; this provides crucial evidence that it might also be possible to repair damaged or lost nerves in other parts of the brain and nervous system. In fact, the ear provides an excellent model for cell transplantation. Dr Sekiya and colleagues have developed a new and much less invasive method to deliver transplanted cells to the nervous system. This method shows that scar tissue which is frequently linked to nerve damage and degeneration in diseases as diverse as hearing loss, motor neurone disease and spinal cord injury can help, rather than inhibit, repair.

      Why is cell transplantation difficult?

      The survival and integration of transplanted cells in the central nervous system is thought to be hindered by scar tissue, which is produced in response to nerve cell damage or loss, by cells called glial cells. This ‘glial scar’ is currently believed to be a major barrier to successful cell transplantation and nerve re-growth. Current practice is to deliver cells directly into the nerve tissue through a fine tube, with the idea being to place cells as close as possible to the site of nerve cell loss. However, this can damage the internal structure of the nerve. In addition, the choice of cells to be transplanted is critical, because different cell types communicate with the biological environment in different ways. Successful transplantation depends on the cells becoming fully integrated into the nerve tissue.

      Why is the ear such a good model for this type of research?

      The key to turning scientific discoveries into clinical treatments depends on being able to measure damage and repair in animal models of a condition, in ways that reflect these processes as they occur in human patients. Hearing loss can occur due to age, genetic mutation, noise damage or the use of various prescribed drugs, all of which can be assessed objectively. Their effects on the structure and function of the ear can be measured at the level of single molecules, individual cells and/or the whole organ in animal models of hearing loss. In this study, Sekiya and his colleagues developed a new animal model of nerve damage in the auditory system, which includes the development of glial scar tissue and replicates the longer term processes underlying nerve damage in human patients. Brain responses to sound and connections between transplanted cells and nerve cells in the brain, as well as with the sensory hair cells in the inner ear, were measured before and after cell transplantation.

      The cells know where to go

      When nerve cells were transplanted into the auditory nerve by injecting them directly into the nerve, the results were disappointing. Most of the cells died within several weeks and there was no sign of hearing recovery. However, some cells that had spilled onto the surface of the glial scar during the transplantation appeared to have moved into the nerve by themselves and survived. The researchers repeated their experiment but this time, they delivered the cells onto the surface of the nerve instead. Surprisingly, many cells entered the nerve tissue and formed connections with the auditory hair cells in the ear and with nerve cells in the brain. The animals’ hearing also improved, suggesting that the transplanted cells had reconnected the ear to the brain.

      What does this mean?

      These results provide hope for patients who might benefit from nerve cell transplantation. They show that the glial scar, originally thought to be a barrier to cell transplantation, contains critical signals for nerve regeneration, and also that cells can be transplanted without damaging the nerve any further. Such a breakthrough could impact on patients with motor neurone disease, for whom suitable donor cells could be applied to the surface of nerves in the spinal cord to restore movement. Similarly, transplanting nerve cells could also be used to reduce the neurological damage which occurs in polio. Transplanted cells can penetrate deep into the central nervous system, which means that the technique could be even more widely applicable.

      Although the number of people with hearing loss who might benefit directly from this therapy is small (as most hearing loss is caused by damage to hair cells, and not auditory nerve cells), this therapy could be used to maintain or regrow a healthy auditory nerve in people receiving cochlear implants, which work best when there is an intact auditory nerve to send signals from the implant to the brain. It’s also likely that the ultimate goal of restoring natural hearing will require that both hair cells and auditory nerve cells are regenerated, so this therapy could be of more use further down the line. What this study shows is that hearing research doesn’t always just benefit those with hearing loss and that investment in hearing research can have a far more wide-ranging impact.

      Find out more

      This work was published in June in PNAS Plus.

      Full Reference: Sekiya T, Holley MC, Hashidoa K, Onoa K, Shimomurac K, Horie RT, Hamaguchia K, Yoshida A, Sakamoto T, and Ito J (2015). Cells transplanted onto the surface of the glial scar reveal hidden potential for functional neural regeneration. Proc Natl Acad Sci.

      To find out more about the research we fund, go to our biomedical research section.

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