Chameleon Spots

该团队将利用有价值的人类细胞类型和被称为Hi-Spot的新培养方法将基础实验室研究转化为生物制药产品。Hi-Spot允许在气液界面的小膜上进行细胞/组织培养，从而使培养具有3D结构质量，并促进更多的生理细胞-细胞相互作用。潜在的理论基础是，这种环境在体外培养环境中产生了更接近体内条件的模拟。反过来，这一改进促进了更强大、更具代表性的技术，以应用于生物制药工作场所进行毒理学筛选和药物发现。就其本身而言，这是一个重大进步。我们应用程序的第二个独特品质来自于我们将为Hi-Spot技术平台带来的高度专业的细胞和组织。我们已经建立的财团将学术界在人类干细胞和原始祖细胞类型方面的专业知识带给南安普顿大学的衍生公司Capsant Technologies(http://www.capsant.co.uk/).细胞类型是关注药物毒性和药物发现的行业的根本利益所在。它们在构成我们的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建立以下人类原代胎儿细胞类型的“Hi-Spot”培养方法：a)神经前体/分化的后代；b)心肌细胞；c)肝细胞；d)和胰腺前体/β细胞。前三种细胞类型显然是毒理学研究的目标。后一种细胞类型对新型胰岛素促分泌剂的药物开发具有重要意义。2.人胚胎干细胞。明格实验室将与分化的人类ES细胞并行工作包1。ES细胞在毒理学筛选方面有很大的兴趣；然而，悬而未决的主要问题之一是，与正常细胞类型相比，它们的分化后代有多大的代表性。这项应用提供了一个难得的机会来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。格雷实验室拥有获取稀有成年海马神经细胞的特权，这些成年海马神经细胞保持增殖能力并充当干细胞。在培养中建立这些细胞并将它们应用于Hi-Spot技术将是神经毒理学筛选的重要一步。4.工作包4将与上述工作包并行运行，并提供对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到位。该工作包还将把专业知识带到96井和384井的格式化系统中。5.最后的工作方案将通过商业评估和面向学术和商业用户的传播计划，开始将我们的知识产权和产品推向市场的进程。总而言之，这些方法提供了一种连贯、清晰的战略，将改进人类文化模型的特权专业知识带入市场，促进商业药物毒理筛选和药物发现的进步。

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.