Cardiac Toxicity Evaluation with a Human Tissue-Engineered Model

Dr. Kareen Coulombe joined us to share her latest findings for assessing cardiac toxicity using a predictive 3D human cardiac microtissue platform for assessing toxicity of chemical compounds.  

What you’ll learn: 

  • How NAM’s are used to assess cardiac toxicity
  • How human 3-D cardiac microtissue systems can address limitations of traditional in vivo and in vitro assays in predicting arrhythmia generation and cardiac toxicity
  • Examples of chemicals impacting the risk of arrhythmia

About our Speaker: 

Dr. Coulombe is co-PI on the NIEHS U01 Bioengineering Research Project at Brown University to develop 3D human microtissue models for environmental toxicity assessment and leads the human cardiac microtissue project with collaborators Dr. Bum-Rak Choi, PhD (RI Hospital) and Dr. Ulrike Mende, MD (RI Hospital).  Coulombe has a Ph.D. in Bioengineering from the University of Washington, won an NIH Pathway to Independence K99/R00 award in 2012, and started her laboratory at Brown University in 2014. She was named a Rising Star by the Cellular and Molecular Bioengineering Group of the Biomedical Engineering Society and was awarded a 2021 NSF CAREER Award. 

Abstract:

Cardiovascular disease is the leading cause of death globally and the World Health Organization estimates that 23% of cardiovascular disease is due to environmental toxicants. However, cardiac toxicity is rarely evaluated for environmental toxicants, despite the availability of advanced cardiac toxicity assessments being available and required for pharmaceutical development. The Coulombe Lab has developed a predictive 3D human cardiac microtissue platform for assessing toxicity of chemical compounds in collaboration with Dr. Bum-Rak Choi (Associate Professor of Medicine, Rhode Island Hospital). Using human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes and primary human cardiac fibroblasts, microtissues have reproducible and mature electrophysiology to predict arrhythmia risk using high resolution optical mapping of voltage and calcium for quantification of the action potential (AP) and calcium transient. This platform has been validated with established ion channel blockers and activators as well as pharmacological agents with known human responses, enabling inference of the mechanisms of action of novel compounds. For example, we have tested bisphenol-A in female cardiac microtissues (1-1000 nM) and found dose-dependent increases in the rate of depolarization and repolarization of the AP, reducing the AP duration by ~50 ms and indicating a moderately increased arrhythmia risk. Thus, this microtissue model of human cardiac tissue is a promising new approach methodology for in vitro toxicity testing for predicting arrhythmia risk in response to environmental toxicants and pharmaceutical compounds to enable safety profile determination.

About ScitoVation:ScitoVation helps clients assess chemical compound safety using innovative science, next-generation technology, and professional expertise. ScitoVation is known for partnership, flexibility, and proven success in its work to develop safer and more effective pharmaceuticals, food ingredients, agricultural chemicals, commodity chemicals and consumer products. A spin-off of the former The CIIT and The Hammer Institutes for Chemical & Drug Safety Sciences, ScitoVation is an industry leader of New Approach Methods (NAMS) for chemical/drug discovery & development in the rapidly evolving global regulatory landscape.