It is a well known fact that many modern drugs have been recalled due to cardiotoxicity. There are a number of models for testing drug cardiotoxicity, and the development of new cell lines has shown potential to enhance these models. One of these cell lines, as recently reported in the June 3, 2015 web edition of Point to Point, the news and information bulletin from SLAS, is the Axiogenesis "Cor.4U human cardiomyocyte product derived from induced pluripotent stem (iPS) cells". This cell line is designed for use "in applications from single cell analysis to high-throughput screening (HTS) of pharmaceutical compounds". Importantly, according to the Axiogenesis news thread, the Cor.4U cell line will be applied to cardiac safety assessment as part of the company's participation in the "The Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative, led by the US Food & Drug Administration (FDA), Safety Pharmacology Society (SPS), Cardiac Safety Research Consortium (CSRC), and the Health & Environmental Sciences Institute (HESI)". The aim of this global initiative is "to improve current regulatory guidance by introducing predictive technologies, including human stem cell-derived ventricular cardiomyocytes, into preclinical safety assessment".
Axiogenesis recently presented a poster titled Analysis of Mitochondrial Function Using Human iPSC-Derived Cardiomyocytes on The Seahorse XF96 Analyzer at the Society of Toxicology (SOT) 54th Annual Meeting, 22-26 March 2015, San Diego CA USA. At the same SOT conference one of our collaborators, Luxcel Biosciences, presented collateral created with us from a poster presentation at SLAS 2015 Optimization of a Multi-Mode Detection Model for Measuring Real-time Cellular Respiration and Mitochondrial Function using Fluorophoric Biosensors.
The Luxcel probes used by BioTek for the SLAS poster and Application Note content measure cellular metabolism in microplate readers, and are an alternative approach to the Seashorse XF96 Analyzer, a high-end closed system, used by Axiogenesis in their SOT poster presentation. Not missing a beat, Luxcel joined up with Axiogenesis and recently demonstrated the merits of the Luxcel approach via data now released in the Application Note Mitochondrial Toxicity Assay in Stem Cell Derived Cor.4U® Cardiomyocytes. Among other conclusions of the Luxcel/Axiogenesis work, the "data illustrate the potential of stem cell derived cardiomyocytes in screening compounds for potential cardiotoxicity using microtitre plate based measurement of both mitochondrial function and glycolytic flux using a human model (Cor.4U®) and the MitoXpress® Xtra - Oxygen Consumption Assay (HS Method) and pH-Xtra® - Glycolysis Assay". An example of their data is shown for the MitoXpress assay below left.
Using HepG2 cells and the Luxcel probes to demonstrate cell metabolic activity in response to compound treatment in a cancer model system, lifetime (µs) data we generated from the BioTek Synergy Neo is shown above right. Similar data for the pH probe is also shown by both Application Notes. The correlation between the Cor.4U cardiomyocytes and the HepG2 cell data would support expansive potential for cell metabolic analysis using the Luxcel probes and a variety of BioTek readers. Think possible!
By: BioTek Instruments, Wendy Goodrich, Applications Scientist