hiPS Derived Assay for Screening Hematopoietic Differentiation Toxicant Effects

用于筛选造血分化毒性作用的 hiPS 衍生测定法

• 批准号: 8618291
• 负责人: Bradley H. Garcia
• 金额: $ 22.45万
• 依托单位: PRIMORIGEN BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-15 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8618291
• 关键词: 2-cyclopentyl-5-(5-isoquinolylsulfonyl)-6-nitro-1H-benzo(D)imidazole; Address; Adult; Affect; African American; Animal Model; Asians; Biological Assay; Brachyury protein; CD34 gene; Cell Density; Cell Differentiation process; Cell Line; Cells; Commit; Critical Pathways; Data; Development; Developmental Process; Dose; Environmental Exposure; Ethnic Origin; Exhibits; Exposure to; Female; Flow Cytometry; Funding; Gene Expression; Generations; Genetic Variation; Guava Fruit; Harvest; Hematopoietic; Hematopoietic System; Hematopoietic stem cells; Hip region structure; Hispanics; Hour; Human; Human Cell Line; Individual; Legal patent; Libraries; Liquid substance; Measures; Mesoderm; Methods; PTPRC gene; Pathway interactions; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Phenotype; Population; Procedures; Process; Propidium Diiodide; Protocols documentation; Publications; Small Business Innovation Research Grant; Source; Staging; Staining method; Stains; System; Systems Analysis; Testing; Toxic Environmental Substances; Toxic effect; Toxicology; Toxin; base; commercial application; cytotoxicity; exposed human population; high throughput screening; human tissue; induced pluripotent stem cell; interest; male; member; notch protein; novel; phase 1 study; phase 2 study; public health relevance; scale up; screening; small molecule; small molecule libraries; toxicant

Primorigen Biosciences (R) Abstract Primorigen Biosciences will use SBIR funds to develop a novel commercial assay that measures the toxicity of compounds on human induced pluripotent stem cells (hiPSCs) differentiating into hematopoietic progenitor cells (HPCs) and on HPCs differentiated from hiPSCs. The assay will rely on Primorigen's highly efficient, patent-pending MesoTotal" medium for differentiating hiPSCs into HPCs. Phase I studies will optimize HPC differentiation and analysis for high-throughput screening formats, determine toxic impact that compounds have on hiPSCs differentiating into HPCs, and screen for compounds that exhibit toxicity towards hematopoietic progenitor cells derived from hiPS cells. In Phase II, we will enhance commercial applications by a) adapting the system to 384-well HTS formats, b) increasing genetic diversity by including additional hiPSC lines, c) testing a larger library and mixtures indicative of typical environmental exposure, and d) completing secondary screenings to establish dosing efficacy and mechanism of actions. In Phase III, the assay system will be evaluated for potential pharmaceutical development applications. The commercial application is a robust scalable human assay system for screening to assess compound toxicity against hiPS cells differentiating into HPCs.

Primorigen Biosciences（R）摘要 Primorigen Biosciences将利用SBIR基金开发一种新的商业检测方法， 测量化合物对人诱导多能干细胞（hiPSC）的毒性 分化成造血祖细胞（HPC）和在从造血祖细胞分化的HPC上， hiPSC。 该测定将依赖Primorigen高效、正在申请专利的MesoTotal培养基， 将hiPSC分化为HPC。 I期研究将优化HPC分化和高通量筛选分析 形式，确定化合物对hiPSC分化成HPC的毒性影响，以及 筛选对来源于以下的造血祖细胞表现出毒性的化合物： hiPS细胞在第二阶段，我们会加强商业应用，包括：a）使系统适应 384-孔HTS形式，B）通过包括另外的hiPSC系增加遗传多样性，c） 测试指示典型环境暴露的较大库和混合物，以及d） 完成二次筛选，以确定给药疗效和作用机制。在 第三阶段，将评价测定系统的潜在药物开发 应用. 商业应用是一种用于筛选以评估 抗hiPS细胞分化成HPC的化合物毒性。