Chameleon Spots

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The team will translate basic laboratory research using valuable human cell types and novel culture methodology called 'Hi-spot' into biopharmaceutical products. Hi-spot permits cell / tissue culture on small membranes at the air-liquid interface permitting 3D structural qualities to cultures and fostering more physiological cell-cell interactions. The underlying rationale is that this environment generates closer mimicry of in vivo conditions within the in vitro culture setting. In turn, this improvement fosters more robust, representative technology to take into the biopharmaceutical workplace for toxicology screening and drug discovery. By itself, this represents a significant advance. The second distinctive quality to our application comes from the highly specialist cells and tissues that we will bring to the Hi-spot technology platform. The consortium that we have established brings expertise in human stem cell and primary progenitor cell-types from the academic sector to the University of Southampton spin-out company Capsant Technologies (http://www.capsant.co.uk/). The cell-types are of fundamental interest to industry focused on drug toxicity and drug discovery. They are discussed in the following work packages that comprise our application. 1. Primary human fetal cells. The Hanley and Wilson laboratories will establish 'Hi-spot' culture methodology from the following human primary fetal cell-types: a) neuroprogenitors / differentiated progeny; b) cardiomyocytes; c) hepatocytes; d) and pancreatic progenitors / beta cells. The first three cell types are obvious targets for toxicology studies. The latter cell-type is of great interest for drug discovery of novel insulin secretagogues. 2. Human embryonic stem (ES) cells. The Minger laboratory will parallel Work Package 1 with differentiated human ES cells. There is great interest in ES cells for toxicology screening; however, one of the main questions hanging over their application is how representative are their differentiated progeny compared to normal cell-types. This application offers a rare opportunity to put them up against normal human primary cell-types. 3. Human adult CNS stem cells. The Gray lab has privileged access to rare populations of adult hippocampal neural cells that retain proliferative capacity and act as stem cells. Establishing these cells in culture and applying them to Hi-spot technology will be a significant step in neurotoxicology screening. 4. Work package 4 will run in parallel to those above and provide validation and exploitation of the academic laboratory research. Fluorescent biochemical and electrophysiological approaches are already in place on microelectrode arrays. This work package will also take the expertise into 96- and 384-well format systems. 5. The final work package will begin the process of taking our intellectual property and products to the market place via commercial assessment and a dissemination programme for academic and commercial users. Taken together, these approaches provide a cohesive, lucid strategy to take privileged expertise for improving human culture models into the market place for advances in commercial drug toxicology screening and drug discovery.