WAT-on-a-chip - Development of a micofluidic, microphysiologic in vitro adipose tissue model for high-throughput drug screening based on hiPSC-derived adipocytes.

WAT-on-a-chip - 开发微流体、微生理体外脂肪组织模型，用于基于 hiPSC 衍生脂肪细胞的高通量药物筛选。

• 批准号: 257256526
• 负责人: Professor Dr. Peter Loskill
• 金额: --
• 依托单位: Healy Laboratory
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/257256526?language=en
• 关键词: WAT; chip; Development; micofluidic; microphysiologic

Drug discovery and development is hampered by high failure rates attributed to the reliance on non-human animal models and non-physiological conditions employed during safety and efficacy testing. A fundamental problem in this inefficient process is that non-human animal models cannot sufficiently represent human biology, and more importantly, they cannot adequately recapitulate human disease states. With the discovery of patient-specific human induced pluripotent stem (iPS) cells, the tissue engineering community is now in position to develop in vitro disease-specific model tissues and organs to be used for high content drug screening and patient specific medicine. The principal goal of this project is to create a white adipose tissue (WAT) model system on a chip. WAT as a model system was chosen since it can play a major role for both drug delivery and efficacy in a variety of ways, including passive drug storage, side-effects of other tissue targeting drugs, and the efficacy of adipose targeted drugs. The WAT-on-a-chip will be based on a microfluidic platform that mimics the dimensions and cellular arrangement of minimal elements of human adipose tissue. This microfluidic design will allow excellent control over media perfusion via continuous flow, which also allows similar control in delivering any soluble drug to the adipose tissue model. Furthermore, the platform will allow for continuous monitoring, sampling, and probing of the tissue model. Secondary goals of this project include (i) the integration of a glucose sensor into the platform to enable live monitoring of glucose level, indicating functionality and drug-response of the tissue, and (ii) differentiation of human iPS cells to functional adipocytes within the developed platform. The final platform is envisioned to be extremely versatile and to be applicable for both fundamental studies of adipose tissue and the screening of drugs for therapeutic diagnostic and applications.

药物发现和开发受到高失败率的阻碍，这归因于对非人类动物模型的依赖以及在安全性和有效性测试期间采用的非生理条件。这种低效过程的一个根本问题是，非人类动物模型不能充分代表人类生物学，更重要的是，它们不能充分概括人类疾病状态。随着患者特异性人诱导多能干（iPS）细胞的发现，组织工程界现在能够开发用于高含量药物筛选和患者特异性药物的体外疾病特异性模型组织和器官。该项目的主要目标是在芯片上创建白色脂肪组织（WAT）模型系统。选择WAT作为模型系统，因为它可以以多种方式对药物递送和功效发挥重要作用，包括被动药物储存、其他组织靶向药物的副作用和脂肪靶向药物的功效。芯片上的WAT-on-a-chip将基于微流体平台，该平台模拟人类脂肪组织最小元素的尺寸和细胞排列。这种微流体设计将允许通过连续流动对介质灌注进行优异的控制，这也允许在将任何可溶性药物递送到脂肪组织模型中进行类似的控制。此外，该平台将允许连续监测、采样和探测组织模型。该项目的次要目标包括（i）将葡萄糖传感器集成到平台中，以实时监测葡萄糖水平，指示组织的功能和药物反应，以及（ii）在开发的平台内将人iPS细胞分化为功能性脂肪细胞。最终的平台被设想为是非常通用的，并适用于脂肪组织的基础研究和治疗诊断和应用的药物筛选。