iPSC technology provides a new and standardized source of differentiated human cells for drug toxicity analysis. Creative Bioarray is dedicated to providing clients with specialized solutions for generating human iPSC-derived cardiomyocytes (hiPSC-CMs) to assess cardiotoxicity/safety during drug development.
Introduction
Unexpected cardiotoxicity leads to high attrition rates during drug development and imposes a significant economic burden on the pharmaceutical industry. In previous drug development, researchers have typically used animals and animal-derived materials in preclinical trials to predict the cardiotoxic effects of new drugs in humans. However, due to species differences and multiple forms of toxicity such as electrophysiological and contractile toxicities, drug responses in animal-derived primary cardiomyocytes for in vitro testing do not accurately mimic the human drug response. The establishment of more predictive human in vitro models is critical for solving this problem.
The limited availability of human cardiac tissues/cells for assessing the cardiotoxic effects of drugs has limited the development of the cardiac field. Recently, the successful reprogramming of human somatic cells into iPSCs provides a promising cell source for drug toxicity assessment. Several reports have already demonstrated the applicability of hiPSC-CMs in assessing the cardiotoxic effects of drug candidates. In conclusion, hiPSCs technology provides a reliable in vitro predictive model for drug screening analysis, which will significantly reduce the risks and costs associated with early clinical trials, leading to a more personalized approach in drug administration.
Fig.1 Setup for drug-induced cytotoxicity and contractility assessment of hiPSC-CMs. (Sharma, 2018)
Solutions for Cardiotoxicity Assessment based on Cell Reprogramming
Creative Bioarray is committed to improving preclinical screening methods to identify cardiotoxic compounds earlier in the drug development process. Given that hiPSC-CMs can be used to screen for drug-induced alterations in cardiomyocyte contractility and electrophysiology, we have developed a "cardiac safety index" (CSI) to serve as a metric for assessing cardiotoxic drugs through high-throughput screening of hiPSC-CMs. Our solution consists of the following steps:
- Derivation of hiPSCs.
- Differentiation of hiPSCs to hiPSC-CMs.
- High-throughput imaging and quantitative viability analysis using hiPSC-CMs.
- High-throughput contractility assessment of hiPSC-CMs.
- Quantification of hiPSC-CM motion for contractility analysis.
- Calculation of a CSI based on hiPSC-CM cytotoxicity and contractility metrics.
Advantages
- Professional and efficient solutions
- Highly trained and experienced technical staff
- High flexibility and cost-effectiveness
As a leading provider of cell reprogramming services, Creative Bioarray is committed to helping our clients achieve early, rapid, and comprehensive toxicity screening of target populations using human iPSC-derived cell lines early in the drug development process. Our specialized technology platform and efficient solutions will accelerate your research in cardiotoxicity assessment. If you are interested in our services, please contact us for more details.
Reference
- Sharma, A.; et al. Use of human induced pluripotent stem cell–derived cardiomyocytes to assess drug cardiotoxicity. Nature protocols. 2018, 13(12): 3018-3041.