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iPSC Derived Cardiac Microchambers for Embryonic Drug Screening

iPSC 衍生的心脏微室用于胚胎药物筛选

基本信息

批准号：
8953685
负责人：
KEVIN Edward HEALY
金额：
$ 23.54万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-06-01 至 2017-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8953685
关键词：
Address Adult Affect Behavior Biochemical Biological Assay Bipolar Disorder Cardiac Cardiac Myocytes Cardiac development Categories Cells Classification Clinical Trials Communities Congenital Abnormality Congenital Heart Defects Cues Data Development Developmental Process Devices Disease Drug Interactions Drug Prescriptions Drug toxicity Drug usage Embryo Embryonic Development Exposure to Fetal Development Fetus Genetic Geometry Heart Heart Diseases Height Human Hypoplastic Left Heart Syndrome In Vitro Left ventricular structure Lithium Medicine Modeling Morphogenesis Myocardium Organ Organogenesis Pathway interactions Patients Pattern Pharmaceutical Preparations Phenotype Physicians Physiological Physiology Population Positioning Attribute Preclinical Drug Evaluation Pregnancy Pregnant Women Regulation Reporting Risk Rodent Role Safety Shapes Structure System Testing Tissue Engineering Tissues Toxicology United States Ventricular Woman Work base biophysical properties cardiogenesis clinical practice commercialization culture plates developmental toxicity drug discovery fetal improved in vitro Model in vivo induced pluripotent stem cell post-market research pregnant prototype public health relevance response screening tissue culture

项目摘要

DESCRIPTION: In this application, we aim to establish an in vitro model to recapitulate early heart development for safety assessment of specific drugs commonly administrated during pregnancy. In aim 1, we will test our hypothesis that cardiac tissue morphogenesis can be modeled in vitro by micro patterning and differentiation of human induced pluripotent stem cells (hiPSCs). We will establish and optimize our in vitro early developing heart model by obtaining a full spectrum of 3D cardiac micro tissues generated from hiPSC patterns with different geometries. In aim 2, we will validate our model by the drugs listed in pregnancy risk categories A and X as negative and positive controls, so we will be able to predict the drug toxicity from categories B-D on early heart development.

产品说明：在本申请中，我们的目的是建立一个体外模型，以重现早期心脏发育的安全性评估特定的药物通常在怀孕期间。在目标1中，我们将测试我们的假设，即心脏组织形态发生可以通过人诱导多能干细胞（hiPSC）的微图案化和分化在体外建模。我们将通过获得由具有不同几何形状的hiPSC图案生成的全谱3D心脏微组织来建立和优化我们的体外早期发育心脏模型。在目标2中，我们将通过妊娠风险类别A和X中列出的药物作为阴性和阳性对照来验证我们的模型，因此我们将能够预测B-D类药物对早期心脏发育的毒性。