Chameleon Spots

该团队将利用有价值的人类细胞类型和称为“Hi-spot”的新型培养方法将基础实验室研究转化为生物制药产品。Hi-spot允许在气液界面处的小膜上进行细胞/组织培养，从而允许培养物具有3D结构质量并促进更多的生理细胞-细胞相互作用。基本原理是，这种环境在体外培养环境中产生更接近体内条件的模拟。反过来，这种改进促进了更强大的，有代表性的技术进入生物制药工作场所进行毒理学筛选和药物发现。这本身就是一个重大进步。我们应用的第二个独特之处在于我们将为Hi-spot技术平台带来高度专业化的细胞和组织。我们建立的联盟将学术界在人类干细胞和初级祖细胞类型方面的专业知识带到了南安普顿大学的分拆公司Capsant Technologies（http：//www.capsant.co.uk/）。细胞类型对专注于药物毒性和药物发现的行业具有根本利益。它们在构成我们应用程序的以下工作包中进行了讨论。1.原代人胎儿细胞。汉利和威尔逊实验室将从以下人原代胎儿细胞类型建立“Hi-spot”培养方法：a）神经祖细胞/分化后代; B）心肌细胞; c）肝细胞; d）和胰腺祖细胞/β细胞。前三种细胞类型是毒理学研究的明显目标。后一种细胞类型对于新型胰岛素促分泌素的药物发现具有极大的兴趣。2.人胚胎干细胞（ES）Minger实验室将与分化的人类ES细胞平行工作包1。人们对ES细胞用于毒理学筛选有很大的兴趣;然而，悬在其应用上的主要问题之一是与正常细胞类型相比，其分化后代的代表性如何。这一应用提供了一个难得的机会，将它们与正常的人类原代细胞类型进行比较。3.人成体中枢神经干细胞格雷实验室有特权获得罕见的成年海马神经细胞群体，这些细胞保留了增殖能力并充当干细胞。在培养中建立这些细胞并将其应用于Hi-spot技术将是神经毒理学筛选的重要一步。4.工作包4将与上述工作包同时进行，并提供学术实验室研究的验证和利用。荧光生物化学和电生理学方法已经在微电极阵列上就位。该工作包还将把专业知识纳入96孔和384孔格式系统。5.最后的工作包将开始通过商业评估和面向学术和商业用户的传播方案将我们的知识产权和产品推向市场的过程。总之，这些方法提供了一个有凝聚力的，清晰的战略，采取特权的专业知识，以改善人类文化模型进入市场的进步，在商业药物毒理学筛选和药物发现。

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.