Clinical Trials in a Dish- hiPSC Cardiomyocyte HTS Electrophysiology System for Detecting Drug Induced Fatal Cardiac Arrhythmias

Dish-hiPSC 心肌细胞 HTS 电生理学系统检测药物引起的致命性心律失常的临床试验

基本信息

批准号：
10552776
负责人：
Travis Jackson Block
金额：
$ 30万
依托单位：
STEMBIOSYS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-01 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10552776
关键词：
Action Potentials Address Adherent Culture Adopted Adoption Animal Model Animals Applications Grants Arrhythmia Biological Assay Calcium Calcium Channel Cardiac Cardiac Myocytes Cardiotoxicity Categories Cell Culture Techniques Cells Clinical Trials Complement Computer software Data Data Analyses Data Set Development Devices Drug Industry Dyes Electrophysiology (science)Extracellular Matrix Feedback Funding Glycocalyx Goals Guidelines Human In Vitro Intellectual Property Ion Channel Legal patent Letters Measures Mission Myocardium National Heart, Lung, and Blood Institute Optics Paper Patients Peer Review Perinatal Pharmaceutical Preparations Phase Phase I Clinical Trials Phenotype Physiology Population Potassium Channel Blockers Preclinical Testing Problem Solving Procedures Production Publications Publishing Recording of previous events Reporting Research Safety Small Business Innovation Research Grant Sodium Channel Source System Technology Testing Tissue Engineering Toxicology Work automated analysis base channel blockers clinical development commercialization cost culture plates data acquisition drug classification drug development drug discovery efficacy testing experience human stem cells improved in vitro testing induced pluripotent stem cell induced pluripotent stem cell derived cardiomyocytes instrument instrumentation machine learning algorithm medication safety meetings monolayer novel patch clamp pre-clinical predictive test prevent programs prototype safety testing scaffold scale up screening software development stem cells voltage

项目摘要

Abstract The goal of this project is to commercialize a novel high throughput cardiotoxicity screening assay based on using human cardiomyocytes. Human cardiomyocytes are obtained from commercial sources of stem cell derived cardiomyocytes, so called hiPSC-CMs. The commercial products to be released by the end of this phase IIb proposal include 1. proprietary extracellular matrix coated cell culture plates (already commercially available - marketed as CELLvo™ Matrix Plus), 2. Cardiotoxicity screening instrument (CARTOX), 3. Optical electrophysiology analysis software to enable HTS data analysis, and 4. Chamber-specific stem cell-derived cardiomyocytes. The FDA and other stakeholders in drug discovery and safety screening are adopting the use of hiPSC-CMs for pre- clinical testing and even for development of clinical trial in a dish approaches. Widespread adoption has been hampered because of limitations surrounding the maturation state of stem cell derived heart muscle and lack of HTS systems for measuring cardiac action potentials. The CARTOX instrumentation and StemBioSys proprietary Matrix Plus products solve these problems and provide further evidence for the adoption of human cell based cardiac assays to replace some animal focused safety screening approaches. The proposed work addresses a large unmet need, both scientifically and commercially.

抽象的该项目的目的是商业化新型高通量心脏毒性筛查测定法基于使用人类心肌细胞。人类心肌细胞可从商业干细胞衍生的心肌细胞的来源，所谓的HIPSC-CMS。商业产品是该阶段IIB提案结束时发布包括1。专有的细胞外基质涂层细胞培养板（已市售 - 以Cellvo™矩阵Plus销售），2。心脏毒性筛选仪器（Cartox），3。光学电生理分析软件可启用HTS数据分析和4。室特异性干细胞衍生的心肌细胞。 FDA和其他在药物发现和安全筛查领域的利益相关者正在采用HIPSC-CMS用于预先临床测试，甚至用于开发在菜肴方法中的临床试验。广泛采用由于围绕干细胞衍生的心脏成熟状态的局限性而受到阻碍肌肉和缺乏用于测量心脏动作电位的HTS系统。卡托克斯仪器和Stembiosys专有矩阵加产品解决这些问题并提供采用基于人类细胞的心脏测定以取代某些动物的进一步证据安全筛选方法。拟议的工作解决了很大的未满足需求并在商业上。