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：
9068913
负责人：
KEVIN Edward HEALY
金额：
$ 11.78万
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/9068913
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 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 Health Heart Heart Abnormalities 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 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.

描述：在本应用中，我们旨在建立一个体外模型，以概括早期心脏发育，以对怀孕期间通常给药的特定药物进行安全评估。在AIM 1中，我们将检验我们的假设，即可以通过微模式和分化人类诱导的多能干细胞（HIPSC）在体外进行心脏组织形态发生。我们将通过获得来自具有不同几何形状的HIPSC模式产生的全频谱来建立和优化我们的体外早期发展心脏模型。在AIM 2中，我们将通过妊娠风险类别A和X中列出的药物验证我们的模型为阴性和阳性对照，因此我们将能够预测B类B-D类别对早期心脏发育的药物毒性。