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，全球约有3.9亿人受影响（IDF糖尿病Atlas 6th Edition，2014年）。大多数糖尿病患者是2型（T2D），通常以胰腺β细胞功能和β细胞量和周围胰岛素耐药性的丧失为特征。尽管当前的疗法确实提供了一定程度的血糖控制，但它们并没有使疾病的长期后果使人衰弱。在正在进行的寻求更好的治疗方法中，现在有关注策略的关注，旨在保留剩余的β细胞或补充β细胞的功能，以支持这一新的糖尿病研究重点，该项目旨在开发人类3D胰腺betacell betacell Health / beta细胞的体外3D模型。目前没有这种商业模型。该模型将使用本地人胰岛和Asterand Bioscience（Asterand's）专有3D细胞培养平台开发。然后，该财团将探索是否可以利用更可持续的细胞来源（例如，IPSC衍生的Beta细胞），并最终使用3D打印可以将其小型模型微型化。 3D打印工作是为了实现高度准确的beta细胞在当前商业平台所基于的井板上的贝塔元素上的分解。调查条件对细胞生存能力和功能的影响将进行研究，以确定最佳的处理条件伪造β细胞。此外，通过分配不同大小的细胞样品来研究细胞群如何影响细胞功能。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，将创造出独特的制造优势，从而可以生产出现成的药物发现产品。