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

开发胰腺 β 细胞健康的 3D 人体体外模型

• 批准号: EP/N510099/1
• 负责人: Jing Yang
• 金额: $ 14.27万
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FN510099%2F1
• 关键词: Development; 3D; human; vitro; model

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.

糖尿病是一个主要的健康问题，全世界约有3.9亿人受到影响(IDF糖尿病地图集，2014年第6版)。大多数糖尿病患者都是2型糖尿病(T2D)，典型的特征是胰岛β细胞功能丧失、β细胞团和外周胰岛素抵抗。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造成的衰弱的长期后果。在不断寻求更好的治疗方法的过程中，目前的重点是保护剩余的β细胞的功能或补充β细胞群的策略。为了支持这一新的糖尿病研究重点，该项目旨在建立一个人体三维胰岛β细胞健康/β细胞增殖模型。目前还不存在这样的商业模式。该模型将使用本地人类胰岛和Asterand Bioscience(Asterand‘s)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，来自iPSC的Beta细胞)，以及最终是否可以使用3D打印将已建立的模型微型化。3D打印工作是为了实现高精度的空间分配，将β细胞分配到目前商业平台所基于的孔板中的膜上。将研究分配条件对细胞活性和功能的影响，以确定分配β细胞的最佳工艺条件。此外，将通过分配不同大小的细胞样本来研究细胞数量对细胞功能的影响。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，将创造独特的制造优势，允许生产用于药物研发的现成产品。