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Engineered pancreatic endocrine cells that report beta cell toxicity for use in high throughput screening applications

Engineered pancreatic endocrine cells that report beta cell toxicity for use in high throughput screening applications
工程化胰腺内分泌细胞可报告 β 细胞毒性,用于高通量筛选应用
批准号:
9201795
负责人:
Erik J Forsberg
金额:
$21.74万
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
已结题
起止时间:
2016-09-16 至 2017-08-31

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中文摘要
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英文摘要
Project Summary/Abstract The prevalence of diabetes in the United States and world-wide is increasing dramatically, and new drugs that can protect or restore the function of insulin-producing pancreatic beta cells are urgently needed. For decades, drug discovery efforts in this space have been hampered by the lack of consistent and abundant human beta cells for drug screening. The advent of beta cells derived from induced pluripotent stem cells (iPSC), as pioneered by Regenerative Medical Solutions (RMS), has opened an era of making readily available beta cells a reality for performing high-throughput screening (HTS) of compound libraries. Considerable market research, including direct customer feedback, has indicated that HTS applications remain expensive and laborious when conducting screening assays of compound libraries to detect insulin, which currently rely upon antibody-based methods such as immunofluorescence microscopy and enzyme-linked immunosorbent assays (ELISA). To further enhance the efficiency of screening thousands of compound libraries for diabetes drug discovery, RMS will engineer iPSC lines for use in HTS assays. Such engineered beta cell products will express a luciferase-green fluorescent protein fusion under the control of the human insulin promoter. This fusion protein, which can be detected by inexpensive and easily automated assays, will enable iPSC-derived beta cells, packaged in RMS’ HTS product platforms, to be a truly accurate, efficient, and cost-effective tool in high-throughput drug screening applications. Direct customer feedback has led to this proposal and addresses their specific utility requirements for performing HTS applications.
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Development of a rapid and inexpensive luciferase-based high throughput screening assay to identify compounds that alter pancreatic β cell function
Diabetes drug screening platforms using patient pancreatic islet-like cells generated from induced pluripotent stem cells
Human Induced Pluripotent Stem Cell-Derived Beta-Cells for Drug and Toxicity Testing
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