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      Improving delivery of stem cells to the inner ear

      This work will bring the testing of stem cell treatments for hearing loss one step closer to clinical trials.

      This is a three-year project led by Professor Marcelo Rivolta at the University of Sheffield. It started in February 2016 and will end in July 2019.

      Background

      The vast majority of hearing loss is caused by irreversible loss of the sensory hair cells and/or their associated auditory nerve cells. Stem cells, capable of turning into any type of cell in the body, could provide a way to treat hearing loss – turning stem cells into hair cells or nerve cells and transferring them into the cochlea could replace the cells that have been lost, and ultimately restore hearing.

      Professor Rivolta and his team in Sheffield have previously used human embryonic stem cells to create a type of ear cell called an ‘otic progenitor’, a cell which is the 'predecessor' of both hair cells and auditory nerve cells. They have used these progenitors to repair damage to the auditory nerve in deaf animals, restoring their hearing.

      However, the use of stem cells in this way raises some safety concerns. Cells could travel beyond the inner ear, and more worryingly, could divide uncontrollably and form tumours.

      One way to stop the cells from spreading beyond the inner ear and to prevent the growth of tumours is to encase them into a suitable material. Such a material should be soft and gel-like to prevent it from damaging the delicate structures in the inner ear; it should be sturdy enough to prevent cells from escaping, while still allowing the nerve cells to communicate with other cells in the inner ear and reconnect hair cells to the brain. Moreover, it should not be toxic, and should allow the stem cells to develop into the necessary nerve cells properly. Encasing the stem cells into gels could also bring other benefits, like protecting them from recognition and destruction by the immune system.

      Project aims

      The researchers will explore how well a particular type of gel, called a ‘worm gel’, meets these requirements. They will test the ability of this gel to limit cell growth while preserving the cells’ health, and they will monitor how well the gel can prevent the cells from escaping from its structure, while still allowing the cells to communicate with the surrounding environment. They will explore the effect of the gel on the ability of the stem cells to turn into auditory nerve cells and test if it protects the cells from the immune system.

      Finally, they will transplant the cell-gel mixture into an animal inner ear, and study how the cochlea responds to it, as well as whether the behaviour of the cells, as tested previously in the lab, is the same.

      Benefit

      The group hopes to be able to use their results to further develop a means to safely and efficiently deliver stem cells to the inner ear, as the next step in the development of a treatment for deafness caused by damage to the auditory nerve. They hope that this research will bring the use of stem cells to treat hearing loss closer to a clinical trial.