I-Corps: Human toxicity assay using synthetic embryo-like structures

I-Corps：使用合成胚胎样结构进行人体毒性测定

• 批准号: 2112458
• 负责人: Jianping Fu
• 金额: $ 5万
• 依托单位: Regents of the University of Michigan - Ann Arbor
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2112458&HistoricalAwards=false
• 关键词: Corps; Human; toxicity; assay; using

The broader impact/commercial potential of this I-Corps project is the development of a controllable and scalable microfluidic technology in which synthetic human embryo-like structures may be derived from human stem cells for quantitative toxicity testing. The development of the proposed technology addresses the need for a cost-effective and highly predictive assay platform to determine embryo toxicology effects. The current assay is conducted using animal models such as rats or mice. These animal tests are costly and have ethical issues and limited predictive powers. The proposed technology offers human-relevant, “organism-level” toxicity testing. The method allows quantitative measurements and perturbations and is compatible with live imaging and high-throughput screens. The proposed technology may use disease- and patient-specific stem cells for disease modeling, and also may allow screening using stem cells derived from different age and racial/ethnic groups, thus modeling responses to pharmacological and chemical compounds of diverse populations.This I-Corps project is based on the development of a controllable and scalable microfluidic technology in which synthetic embryo-like structures derived from human stem cells may be utilized for embryo toxicity testing. The proposed microfluidic device allows precise positioning of human stem cell colonies in prescribed locations within the microfluidic device. In addition, the proposed device allows precise temporal delivery of soluble factors to drive these human stem cell colonies to develop and organize into multicellular structures whose molecular and cellular features bear significant similarities to early post-implantation human embryos. The proposed technology has been shown to be controllable, reproducible, scalable, and compatible with live imaging and immunocytochemistry, which may allow easy adoption into the existing high-throughput toxicity screening pipelines. The technology is designed to provide high-content phenotypic and morphological profiling of the effects of pharmacological compounds on embryo development based on colorimetric/fluorescent reagents.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

该I-Corps项目的广播电源影响/商业潜力是开发控制器和可扩展的微流体技术，其中合成的人类胚胎样结构可以从人类干细胞中得出，以进行定量毒性测试。拟议技术的发展解决了对确定胚胎毒理学效应的经济高效且高度预测的测定平台的需求。当前的测定是使用大鼠或小鼠等动物模型进行的。这些动物测试是昂贵的，并且存在道德问题和有限的预测能力。拟议的技术提供了与人类相关的“生物水平”毒性测试。该方法允许定量测量和扰动，并且与实时成像和高通量屏幕兼容。 The proposed technology may use disease- and patient-specific stem cells for disease modeling, and also may allow screening using stem cells derived from Different age and racial/ethnic groups, thus modeling responses to pharmaceutical and chemical compounds of divers populations.This I-Corps project is based on the development of a controller and scalable microfluidic technology in which synthetic embryo-like structures derived from human stem cells may be utilized for embryo toxicity测试。所提出的微流体装置允许精确定位在微流体设备内规定的位置中的人类干细胞菌落。此外，提出的装置允许精确暂时递送固体因子，以驱动这些人类干细胞菌落发展并组织成多细胞结构，其分子和细胞特征与早期植入后人类胚胎具有显着相似之处。该提出的技术已被证明是可以控制，可重现的，可扩展的，并且与实时成像和免疫细胞化学化学相兼容，这可能使现有的高通量毒性筛选管道可以轻松采用。该技术旨在提供基于比色/荧光试剂的胚胎化合物对胚胎开发的影响的高含量表型和形态学分析。该奖项反映了NSF的法定任务，并被认为是通过基金会的知识分子优点和更广泛的影响审查的审查标准来通过评估来通过评估来获得的支持。