In Vitro Cardiotoxicity Testing

The majority of studies performed by HemoGenix® incorporate a Complete Service, Full Report that can be used for an IND application. More recently, Sponsors have requested a more streamlined study and studies involving high-throughput screening. For this reason, HemoGenix® now provides 3 types of study format. 

1. Complete Service, Full Report Study: Fully customized study that includes the Study Plan, Draft Text and Final Text Report with QA audit.
2. Rapid Toxicity Study: A customized study that includes the Study Plan and full protocol, raw results and graphical data in a single Excel Workbook. No formal text report and no QA audit is performed. This type of study is designed for early drug development. No interpretation or conclusions are provided.
3. High-Throughput Screening Study (presently only available for human studies): A screening study is designed for high-throughput screening of compounds during ADME/Tox screening in multiples of 5 on specific cell populations to provide the most important ranking information. The full protocol, raw results and graphical data are provided in an Excel Workbook. No interpretation or conclusions are provided. This type of Screening Study is part of the ComparaTOX™ HT Platform.

Prior to the introduction of embryonic stem (ES) or induced pluripotential stem (iPS) cell-derived cardiac myocytes, also called cardiomyocytes, it was virtually impossible to study the effects of in vitro, human drug-induced cardiotoxicity, the results of which could be extrapolated to human clinical trials. All studies had to be performed on animal tissues, which do not provide the best extrapolation models for the human situation. This does not mean that ES- and iPS-derived heart cells are flawless. Nevertheless, these and other primary in vitro models have become part of the in vitro toxicity testing paradigm.

With the introduction of standardized and validated ATP bioluminescence in vitro toxicity assays starting with HALO®-Tox HT for hematotoxicity testing in 2002, HemoGenix® has developed a number of in vitro toxicity testing assay platforms. CardioGlo™-Tox HT, RenalGlo™-Tox HT and SkinGlo™-Tox HT are now being added to the list of in vitro toxicity testing platforms that can be used in parallel with each other, since they all use the same readout. This extended toxicity testing platform is called the ComparaTox™ Platform.

• Cardiomyocytes, like hepatocytes, produce high concentrations of intracellular ATP (iATP) due to their high metabolic activity. Changes in iATP concentration directly correlate with cellular and mitochondrial integrity and cytotoxicity.
• Cardiomyocytes from various sources and species can be used with CardioGlo™-Tox HT.
• CardioGlo™-Tox HT incorporates a validated ATP bioluminescence readout to measure cardiotoxicity.
• CardioGlo™-Tox HT is a calibrated and standardized assay platform that allows results to be directly compared between different drugs, cardiomyocyte sources and species over time.
• High-throughput capability using 96- or 384-well plate formats allows ADME-Tox drug or compound screening, thereby significantly reducing unexpected results during pre-clinical testing.
• Cardiotoxicity contract research studies can be performed using different oxygen tensions that simulate different physical conditions.
• CardioGlo™-Tox HT can be used to investigate cellular drug-drug interactions or multiplexed with assay readouts.
• Incorporates the most sensitive ATP bioluminescence readout available.
• Study Turnaround time: Usually within 4-5 days.
• Validated assay readout according to FDA Bioanalytical Method Guidelines.
• Supports the 3Rs (Reduction, Refinement, Replacement) assay platform for animal testing.

• Fresh
• Cryopreserved
• ES- and/or iPS-derived
• Cardiomyocyte cell lines

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CardioGlo™-Tox HT can be used with cardiomyocytes from a variety of animal species. For human, most studies are performed using ES- or iPS-derived cardiomyocytes.

Please contact HemoGenix® for more information.

• Membrane integrity: LDH or PI dye exclusion
• Apoptosis: Biochemical caspase detection
• Mitochondrial dysfunction: Mitochondrial ToxGlo™
• Glutathione Assay (GSH): Oxidative stress
• OxyFLOW™: Oxidative DNA damage

Please also view the Mechanism of Action page.

This unique in vitro toxicity testing platform called ComparaTOX™. It is based on the fact that other HemoGenix toxicity assays use exactly the same readout, namely a standardized and validated ATP bioluminescence signal detection system. For example, HALO®-Tox HT, ImmunoGlo™-Tox HT, MSCGlo™-Tox HT, HepatoGlo™-Tox HT and NeuroGlo™-Tox HT. Although each assay platform has been designed for a different biological stystem, they all use the same readout. When combined together into the ComparaTOX™Platform, the results from each assay platform can be directly compared with each other. This allows the response to drugs and other agents to be ranked according to:

1. Drug toxicity
2. Cell type
3. Species

You can perform in vitro cardiotoxicity testing in-house using assay kits sold by Preferred Cell Systems™. Please click on the links below to take you to the assay kit page on the Preferred Cell Systems website. 

• CardioGlo™-Tox HT