Stem Cell Therapy for Sensorineural Hearing Loss - How Do Glial Cells Interact With Auditory Stem Cells in the Peripheral Auditory System?

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Clinical Background of ResearchHearing problems are an extremely significant public health issue. Almost 10 million people in Britain suffer with hearing impairment and forecasts suggest this will rise to 15 million by the year 2030. 'Sensorineural hearing loss' accounts for almost 90% of all hearing problems and occurs as a result of irreversible damage to the inner ear, especially the cochlea, where sound vibrations are converted into nerve signals. Although electrical devices such as Cochlear Implants have been used successfully to help patients of all ages suffering with severe sensorineural hearing loss, the limitations of such devices are gradually becoming apparent. Regenerative medicine provides some hope of biological therapies which may be able to treat sensorineural hearing loss with greater effect than current treatments with electrical devices. In a recent major breakthrough, our laboratory has demonstrated the ability of stem cells to repair and restore function of damaged hearing nerves in animal models of sensorineural hearing loss. This project will build on our previous work by understanding how stem cells integrate with a damaged hearing system. Importance of this Research'Glial Cells' are cells which maintain the health of nerve cells. It is well known that nerve damage results in the activation and multiplication of 'glial cells'. In some parts of the nervous system, this process of glial cell multiplication can help with the repair of damaged nerves, but in other parts, such as the brain and spinal cord, the multiplication of glial cells represents scarring which limits further damage to nerves, but also prevents repair. It has recently been discovered that damage to the hearing nerve also causes multiplication of glial cells, but it remains unclear if this represents an environment which would either support repair or whether it represents scarring. This would obviously have implications on the ability for stem cells to repair the damaged hearing nerve. Hence, understanding the relationship between the glial cells of the hearing system and stem cells is a key factor in the quest to translate this therapy to patients. Aims of this ResearchThe aims of this project are to understand the ways in which stem cells communicate with glial cells, and to illustrate whether the response of glial cells to damage of the hearing nerve represents scarring, or whether it represents a favourable environment for and stem cells to repair the hearing nerve. We will then demonstrate how transplanted auditory stem cells integrate with glial cells in animal models of deafness. Research PlanThe project will be conducted in two phases. The first phase will consist of culturing stem cells programmed for the auditory system to check if they are capable of producing their own glial-like cells. The stem cells will then be cultured alongside glial cells from the cochlea, which will allow the interaction between the two cell types to be studied. The second phase will consist of determining whether stem cells are able to repair the damaged hearing nerve despite the multiplication of glial cells. This will involve performing careful analysis of the glial cell types in the damaged hearing nerve and how stem cells interact with them. The information gathered from the previous phase will help in describing this relationship. Host InstitutionThis project will be undertaken at the Centre for Stem Cell Biology at the University of Sheffield which has international recognition as a centre of excellence for research into Stem Cells. The centre has pioneered the use of stem cells to the inner ear and has all the necessary facilities to carry out this project.