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

基本信息

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
项目类别：
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

项目摘要

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.

原始生物科学（R）摘要 Frimorigen Biosciences将使用SBIR资金开发一种新颖的商业测定法测量化合物对人诱导的多能干细胞（HIPSC）的毒性区分造血祖细胞（HPC）和HPC上的HPC hipscs。该测定法将依赖于Primorigen的高效，申请专利的中介” 将HIPSC区分为HPC。第一阶段研究将优化HPC的分化和分析，以进行高通量筛选格式，确定化合物对HIPSC的毒性影响，并确定分化为HPC的HIPSC，以及筛选出对造血祖细胞毒性的化合物的筛选臀部细胞。在第二阶段，我们将通过a）调整系统来增强商业应用 384孔HTS格式，b）增加遗传多样性，包括其他HIPSC线，c）测试较大的文库和指示典型环境暴露的混合物，D）完成次要筛选以确立剂量功效和作用机理。在第三阶段，将评估测定系统的潜在药物开发申请。商业应用是可筛选的可伸缩人类测定系统，以评估对臀部细胞分化为HPC的复合毒性。