A microfluidic model of the neurovascular unit for stroke research

Dr Paul Holloway
Research Fellow 2017

Dr Paul Holloway
University of Oxford

Despite significant research efforts Stroke remains a leading cause of death worldwide.  New approaches to drug discovery utilising cutting edge cell patterning technologies, may accelerate the identification of an effective treatment.  this project will develop a novel cellular model of the brain using “Organ on chip” technologies to enable new possibilities in stroke research.

Stroke causes 4.4 million deaths annually and is the largest cause of adult disability worldwide.  A blockage of blood flow to the brain starves brain cells of nutrients and oxygen, leading to the destruction of an estimated 1.9 million neurons every minute.  However despise significant research efforts, 1026 candidate neuro-protective stroke therapies have failed to reveal a treatment.  Whilst animal models have enabled significant medical advances, 70 million years of evolution separate humans from rodents.  As such, the possibility of therapeutic targets being present in humans but not in rodents, should not be overlooked.  Cell culture offers huge experimental power in the ability to precisely investigate human cellular function, whilst enabling high throughput experimentation.  However, a study performed by O’Collins et al., 2006 found that of 1026 therapeutic agents tested pre-clinically for stroke only 24 were tested in experiments including cell culture models.  This is largely due to the lack of a cell culture model for stroke that recapitulates the complex interactions between brain and blood vessel in stroke.

Recently, micro-fabrication techniques adopted from the semi conductor industry have allowed the production of miniaturised biological devices for complex, spatially-defined cell culture which can be used to mimic human organs.  this ‘Organ on chip’ technology represents a paradigm shift in the way scientists can investigate disease and test new drugs in human cells.  This project will use microfluidic technologies to create a 3D miniaturised model of the brain using human cells.

"Stroke causes 4.4 million deaths annually"
Device size vs 5p coin

Device size vs 5p coin

This model will enable brain cells to be grown in 3D, fed by artificial blood vessels which can be blocked using precisely defined miniature clots to mimic stroke.  This will enable more effective research into the best possible drugs to treat stroke, aiding translation of drugs from ‘bench to bedside’ and also reduce the number of animals used to test drugs.

This project will utilise a novel method which takes advantage of capillary action and liquid surface tension to pattern a three dimensional environment for cell growth with micron (a thousandth of a millimeter) scale precision in a simple operation.  This method will be utilised to establish a ‘brain on chip’ devise which will be extensively characterised in the disease relevant context of stroke to provide a powerful new platform for drug discovery.