Adding new dimensions to invitro models of stroke and cSVD
Dr Paul Holloway Principle Investigator Radcliffe Department of Medicine, University of Oxford
Host: Dr Allesandra Granata
A light lunch will be provided from 12:30.
Stroke is the largest cause of adult disability in the world and despite over 1000 prospective neuroprotective agents having been investigated pre-clinically, none have yet translated to the clinic. A number of key differences in the neurobiology of animal models and humans exist at both the cellular and molecular level, providing impetus to study human based systems. However, human in vitro stroke models are typically limited to simplistic monolayer cell cultures which fail to recapitulate the high level of structural organisation in the brain, 3D heterotypic cellular interactions and spatio-temporal localisation of injury. In his lab Dr Holloway is using a range of techniques from iPSC and organoid cultures to microfluidic systems, to model and investigate specific aspects of stroke injury. Dr Holloway’s talk will give an overview of how these different approaches can be used to model neuronal circuits and gliovascular interactions, along with examples of how these systems can provide novel insights into disease mechanisms and therapeutic opportunities.
Paul's research utilises microfluidic technologies to precisely define the cellular micro-environment and enable new insights into neurovascular biology.
In the brain, endothelial cells, perivascular cells, glia and neurons are intimately coupled, enabling tight regulation of the blood brain barrier, responses to metabolic demands, and inflammatory status. This has lead to the consideration of these cellular elements as part of a functional unit termed the 'neurovascular unit'. Disruption of this system is evident in many human neurological disorders. However, investigating this system in humans and modelling the complex interactions in vitro is particularly challenging.
Recently, micro-fabrication techniques adopted from the semiconductor industry have allowed the production of miniaturised biological devices for complex, spatially-defined cell culture which can be used to mimic human organs. As part of my Royal Commission Research Fellowship, at the University of Oxford’s Laboratory of Cerebral Ischemia, I am utilising ‘Organ on chip’ technologies to develop a three-dimensional, dynamic, heterotypic cellular model of the neurovascular unit. The pathophysiological relevance of this model will be interrogated in the context of stroke, testing the fidelity of cellular coupling and interaction by metabolically perturbing the system.
It would be great to see you in person, but if you need to attend remotely please contact Jane Sugars to receive a Zoom link.
