Development of a 3D human in vitro model of pancreatic beta cell health

糖尿病是全球约3.9亿人的主要健康问题（IDF糖尿病地图集第6版，2014）。大多数糖尿病患者为2型（T2D），典型特征是胰腺β细胞功能和β细胞质量的丧失以及周围胰岛素抵抗。虽然目前的治疗方法确实提供了一定程度的血糖控制，但它们并不能防止这种疾病的长期衰弱后果。在持续寻找更好的治疗方法的过程中，目前的重点是旨在保持剩余β细胞功能或补充β细胞质量的策略。为了支持糖尿病研究的这一新重点，该项目旨在开发胰腺β细胞健康/ β细胞增殖的人体3D体外模型。目前还不存在这样的商业模式。该模型将使用天然人类胰岛和Asterand生物科学公司专有的3D细胞培养平台进行开发。然后，该联盟将探索是否可以利用更可持续的细胞来源(例如。（ipsc衍生的β细胞），以及最终是否可以使用3D打印将所建立的模型小型化。3D打印的工作是将β细胞精确地分配到孔板上的膜上，这是目前商业平台的基础。分配条件对细胞活力和功能的影响将被研究，以确定分配β细胞的最佳处理条件。此外，将通过分配不同大小的细胞样本来研究细胞群体如何影响细胞功能。拟议的细胞打印解决方案与两个工业合作伙伴开发的技术相结合，将创造一个独特的制造优势，允许生产用于药物发现的现成产品。

Diabetes mellitus is a major health issue with ~390 million people affected worldwide (IDF Diabetes Atlas 6th edition,2014). Most diabetics are type 2 (T2D), typically characterised by the loss of pancreatic beta cell function and beta cellmass and peripheral insulin resistance. Whilst current therapies do provide some level of glycaemic control, they do notprevent the debilitating long-term consequences of the disease. In the on-going search for better treatments, there is now areal focus on strategies that aim to preserve the function of remaining beta cells or replenish beta cell mass.To support this new focus of diabetes research, this project aims to develop a human 3D in vitro model of pancreatic betacell health / beta cell proliferation. No such commercial model currently exists. The model will be developed using nativehuman islets and Asterand Bioscience's (Asterand's) proprietary 3D cell culture platform. The consortium will then explorewhether a more sustainable cell source can be utilised (eg., iPSC-derived beta cells) and ultimately whether theestablished model can be miniaturised using 3D printing. The 3D printing work is to achieve highly accurate spatialdispensing of beta cells onto membranes in well plates that the currently commercial platform is based on. The effects ofdispensing conditions on cell viability and functions will be investigated to identify an optimal processing condition fordispensing beta cells. In addition, how cell population influences cell function will be studied by dispensing cell sampleswith different sizes. The proposed cell printing solution combined with technologies developed by two industrial partners willcreate a unique manufacturing advantage allowing the production of off-the-shelf products for drug discovery.