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

摘要 该项目的目标是将一种新的高通量心脏毒性筛选试验商业化。 基于对人类心肌细胞的研究。人的心肌细胞是从商业 干细胞来源的心肌细胞，即所谓的hiPSC-CMS。即将推出的商业产品 本阶段发布的iib提案包括1.专有的细胞外基质涂层细胞 培养板(已上市--销售名称为CELLvo™基质Plus)，2.心脏毒性 筛查仪(CARTOX)，3.启用HTS数据的光学电生理分析软件 分析，以及4.小室特异性干细胞来源的心肌细胞。FDA和其他机构 药物发现和安全筛选方面的利益相关者正在采用HiPSC-CMS进行预 临床试验，甚至用于开发临床试验中的DISH方法。广泛采用 由于干细胞来源的心脏的成熟状态的限制而受到阻碍 肌肉和缺乏测量心脏动作电位的HTS系统。CARTOX 仪器和StemBioSys专有的Matrix Plus产品解决了这些问题，并提供 采用以人类细胞为基础的心脏分析取代某些动物实验的进一步证据 安全筛查即将到来。这项拟议的工作解决了一个巨大的未得到满足的需求，这两个方面都是科学的 商业上也是如此。

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.