Designer in vitro neural circuits for assessment of regenerative therapies.
PhD Supervisor(s): Rose Fricker; Paul Roach
The interconnectivity between the plethora of neuronal cells that make up the central nervous system make replication of such systems in vitro extremely difficult. As such, there is a lack of robust in vitro neuronal models to explore neural degeneration in reference to disease or aging; or screen pharmaceutical, cellular or molecular therapies. In vivo models are beset with high costs, lengthy complex analyses, and ethical issues with using animals, whilst cell culture models can only give limited information on how cells function in relation to each other, and particularly how a neural circuit is affected. The design of an in vitro ‘test-bed’ would need to have an ability to continuously monitor cell/ tissue response to exerted stimuli, with functional assessment of the living neural circuits being key to understanding the impact of the stimuli. Robust and reliable manipulation of cell populations, making up part(s) of the neural circuitry, is necessary to give accurate read-outs for the screening of new therapies.
Advances in, and adaption of technology from other industries has now allowed the production of well-defined living neural circuits on lab-on-a-chip platforms. We have established a platform for the fabrication of these well-defined neural circuits, with current specific focus on the Huntington’s disease model although funding is in place for this to be expanded into the Parkinson’s disease model. Using a microfluidics approach we have been able to house selected neural cell types and promote directional connectivity – forming a defined neural circuit, Figure1. We will further develop this technology to address specific questions regarding protection/ treatment of diseased/ aged neural tissue.
