In their own words: NSMI-funded scientists on their groundbreaking work

North Staffordshire researchers undertake innovative brain injury study involving surgeons and scientists

In a new study started in 2017, a North Staffordshire research team has succeeded in keeping adult human brain tissue alive in a dish outside of the body, using samples of tissue donated by living patients undergoing surgery for a brain condition called ‘Chiari malformation’.

Clinical lead for the study, consultant neurosurgeon Mr Nikolaos Tzerakis explained: “The Chiari malformation is a fairly common problem in Neurosurgical practice. Simply put, the part of the brain at the back of the head which is called the cerebellum, lies lower than the normal level.

“This creates crowding in a tight bony space called foramen magnum, which then causes some difficulty in the circulation of the brain fluid. Patients with Chiari malformation present with headaches mostly during coughing, laughing and straining.

“When surgical treatment is required the usual operation is called Foramen Magnum Decompression, during which we remove a small part of the bone at the back of the head and the spine. On a few occasions, some cerebellar tissue has to be removed to allow adequate decompression and circulation of the brain fluid.

“This sample would have been of no use until now because according to the classical surgical protocol it is removed and disposed. However, this tissue has living nerve cells and they can be grown in the laboratory without any additional risk to the patient.”

Patients with Chiari malformation are widely believed to have essentially healthy (viable) tissue because the brain tissue is misplaced rather than diseased. In the past, scientists studying the human brain have been limited by the difficulty in obtaining tissue for such studies. Their options have been limited to samples removed post mortem – which can quickly die – or tissue from cancerous or diseased brains.

Proving the successful use of Chiari tissue in a dish has the potential to be a very useful new scientific development, which could help in the study and discovery of new treatments for brain injuries and diseases which could be investigated using such a model.

Before they could start their research, the scientists went through a three-year planning process including an exhaustive review within the NHS to make sure their methods were ethical.

They sought consent from a number of patients, some of whom agreed for their cerebellar tissue to be kept for the research study, rather than be incinerated, as would be the normal practice.

Clinical Lecturer Mr Jon Sen, a neurosurgeon, said: “It made me think ‘why has no one thought of doing this before?’ The simplest ideas are often some of the best ones, but it still took a lot of banging our heads together in the neurosurgery department to reach the idea of trying to obtain tissue from our Chiari patients. #

“A key issue is that Chiari is the only surgery we ever do where we take out brain tissue that we could consider within a ‘normal’ enough limit that we could develop a meaningful tissue injury model from.”

The study – supported by a grant from the North Staffordshire Medical Institute – is being led by Professor of Neural Tissue Engineering at Keele’s medical school, Divya Chari.

This new scientific advance also has the potential to reduce the need for animal testing, and could allow the Keele University scientists to simulate the effects of injuries on brain tissue in a laboratory environment.

Prof. Chari said: “I feel passionate about the need for models to reduce animal experimentation. In my early training, I learned to reproduce brain and spinal cord injuries in rodents so I know first-hand the major ethical and technical difficulties these have.

“In animal models there’s potential for substantial suffering – they can lose movement and bladder control, become quadriplegic.

“Our aim is to develop a successful dish model for use in laboratories, that’s relevant to human injuries. We’ve previously proven we can develop models in a dish using tissue derived from rodents, but this is the first time we’ve done it using human tissue.

“Make no mistake, this is a huge undertaking and the success of the work relies on collaboration of a big team working across the hospital and laboratory units. This includes neurosurgeons Mr Nikolaos Tzerakis and Mr Rupert Price, research nurse Holly McGuire and scientists Dr Jacqueline Tickle and Dr Christopher Adams at Keele University.”

The study was a long time in the planning, however, the process accelerated rapidly when the team finally received their first tissue sample this summer.

Researcher Dr Jacqueline Tickle said: “The time for collection from the patient and processing in the laboratory was less than an hour. It has to happen very quickly so there’s less time for the tissue to die and it remains viable.”

The tissue samples were cut into slices of varying thickness to examine the tissue survival and observe major brain cell types.

At first the researchers had no idea what to expect.

Prof. Chari said: “The fact that we have seen tissue survival for well over two weeks made us excited because we had no idea whether we could get it to remain viable for even 24 hours. The fact that we can detect the major cell types present in the brain is very positive”

“When an incision was made in one of the samples to replicate an injury, the researchers believe they can see some changes that are typical of genuine brain injuries.”

Prof. Chari and Mr Sen added: “This is still very, very early. We’ve only got the tissue from two patients so far. Getting the tissue depends on many factors- whether the patient consents to donating the sample, whether the surgery goes ahead as planned, and ultimately whether the surgeon makes the decision to remove the tissue.”

“So we are in it for the long haul, but we all believe it is worth the effort, because the first results are pretty exciting. The main outcome at this stage is that we’re confident that the tissue can remain viable for a relatively long time, if the conditions are kept right.

“It suggests that we could make an injury model in these tissue samples and then look at responses to therapeutic manoeuvres.”

Professor Shaughn O’Brien, chairman of the North Staffordshire Medical Institute, said: “This is an outstanding research project and a unique and clever approach to the study of neural/brain tissue which will attempt to replicate the real life situation in human tissue but without being in any way additionally invasive for any patients.”

The North Staffordshire Medical Institute is a charity funded by public donations that provides grants for vital medical research in the Staffordshire area.

To find out more about their work, visit nsmedicalinstitute.co.uk.

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