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

• 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
• 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

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 该项目的目标是将新型高通量心脏毒性筛选试验商业化 基于使用人心肌细胞。人心肌细胞是从商业获得的。 干细胞衍生的心肌细胞的来源，即所谓的 hiPSC-CM 的商业产品。 在此 IIb 阶段结束时发布的提案包括 1. 专有的细胞外基质涂层细胞 培养板（已市售 - 商品名为 CELLvo™ Matrix Plus），2. 心脏毒性 筛查仪（CARTOX），3. 光学电生理分析软件，支持 HTS 数据 分析，以及 4. FDA 和其他腔室特异性干细胞衍生的心肌细胞。 药物发现和安全筛选的利益相关者正在采用 hiPSC-CM 进行预 临床测试，甚至在培养皿中进行临床试验的方法得到广泛采用。 由于干细胞来源心脏成熟状态的限制而受到阻碍 肌肉和缺乏用于测量心脏动作电位的 HTS 系统。 仪器和 StemBioSys 专有的 Matrix Plus 产品解决了这些问题并提供 进一步证据表明采用基于人体细胞的心脏检测来替代一些以动物为中心的检测 拟议的工作从科学角度解决了巨大的未满足需求。 和商业上的。