Sensory neuroscience to develop novel treatments

Matthew HolleyGroundbreaking and interdisciplinary neuroscience conducted at the University of Sheffield, is the key to discovering the secrets of the brain and the mind and helping people in our ageing population to live well for longer.

Although brain research is an extremely intricate and often a painstaking process a chance discovery during a transplant experiment on the ear using cell lines developed by Sheffield researchers could have profound implications for helping restore the function of neurodegenerative disorders such as Alzheimer’s and Motor Neuron Disease (MND).

The delicate operation, which took place in Japan, was the culmination of a long collaboration between biomedical scientist, Professor Matthew Holley, and Neurosurgeon Dr Tetsuji Sekiya at Kyoto University’s Graduate School of Medicine.

“He did all the really hard stuff,” said the modest Professor Holley whose work has been funded by Action on Hearing Loss and the Wellcome Trust.

"Dr Tetsuji is a brilliant surgeon. He can carefully compress the nerve in the ear, which causes hearing loss similar to that in man, inject replacement cells with great precision and then measure recovery.

"The really hard part is then to section the tissue and to label all the cells we put in. This provides proof that the injected cells reconnect the sensory ‘hearing’ cells to the brain.”

During the first experiments, the two scientists made a startling discovery. The glial scar created by compressing the nerve had previously been regarded as an obstacle to regeneration. When the surgeon injected cells into the nerve – a commonly tested procedure known as intra-neural transplantation – there was no recovery.

We had stumbled upon the possibility of a new, non-invasive technique to transplant cells into the nervous system. We showed that the glial scar, rather than an obstacle to regeneration, can actually provide critical cues to the integration of donor cells.

Professor matthew holley

“The results were disappointing,” said Dr Sekiya. “Most of the cells died within several weeks and there was no sign of functional recovery, which we measured by recording the brain’s response to sound.”

But then they noticed something unexpected.

Some of the cells that had spilled onto the surface of the glial scar appeared to have migrated into the nerve by themselves and survived.

Professor Holley added: “This chance observation led us to repeat the experiment but to change the delivery by leaving the glial scar intact and placing the cells onto the surface.

“To our surprise they burrowed into the nerve and formed functional connections between the auditory sensory cells in the ear and the cells in the hindbrain.

“We had stumbled upon the possibility of a new, non-invasive technique to transplant cells into the nervous system. We showed that the glial scar, rather than an obstacle to regeneration, can actually provide critical cues to the integration of donor cells.”

The results provide hope for patients who might benefit from nerve cell transplantation.