Use of human Induced Pluripotent Stem Cell-Derived Cardiomyocytes to Predict the Cardiotoxicity Potential of Next Generation Nicotine Products.

Introduction:
This text discusses a study that aimed to predict the cardiotoxicity potential of next generation nicotine products (NGPs) compared to cigarettes using a human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) assay. The assay, called the Cardio quick Predict, uses metabolomics to screen for potential structural and functional cardiac toxicants based on changes in four metabolites.

Key Points:

* The study exposed hiPSC-CM to smoke or aerosol bubbled PBS samples from reference cigarettes, heated tobacco products (hTPs), and electronic vaping products (EVPs).
* The assay predicted the concentration at which a sample shows cardiotoxicity potential (cTP) using a prediction model.
* Nicotine tested in isolation was predicted to have cardiotoxic potential at concentrations greater than 80 μg/mL.
* The 1R6F reference cigarette bPBS was the most active, followed by hTP bPBS, which displayed cardiotoxic potential at a 10 times higher concentration.
* None of the EVP bPBS samples were active in the assay up to the maximal concentration tested.
* The study showed that this assay is sensitive and robust for the assessment of different NGPs and may be considered as part of a larger overall scientific framework for NGP assessments.
* The implementation of rapid screening assays that can identify functional and structural cardiotoxicity earlier in the drug development pipeline has been shown to have the potential to improve safety and the cost and time required to bring new drugs to market.

Main Message:
The main message of this text is that the Cardio quick Predict assay can be used as a rapid screening tool to assess the cardiotoxicity potential of NGPs and that this technique may be considered as part of a larger overall scientific framework for NGP assessments. The study found that NGP aerosols have a relatively simple chemical composition with fewer and substantially reduced levels of harmful and potentially harmful components compared to tobacco smoke. additionally, nicotine tested in isolation was predicted to have cardiotoxic potential at concentrations greater than 80 μg/mL, which is higher than expected physiological levels associated with combustible cigarette smoking. The study suggests that the assay may be useful for regulatory purposes in assessing the cardiotoxicity potential of NGPs.

Simms L, Yu F, Palmer J, et al. Use of human Induced Pluripotent Stem Cell-Derived Cardiomyocytes to Predict the Cardiotoxicity Potential of Next Generation Nicotine Products. Frontiers in toxicology. 2022;4:747508. doi:10.3389/ftox.2022.747508