Automated Sarcomere Structure Analysis for Studying Cardiotoxicity in Human Pluripotent Stem Cell-Derived Cardiomyocytes

Microscopy and Microanalysis, vol. 29, pp. 254–264

Abstract

Abstract Drug-induced cardiotoxicity is one of the main causes of heart failure (HF), a worldwide major and growing public health issue. Extensive research on cardiomyocytes has shown that two crucial features of the mechanisms involved in HF are the disruption of striated sarcomeric organization and myofibril deterioration. However, most studies that worked on extracting these sarcomere features have only focused on animal models rather than the more representative human pluripotent stem cells (hPSCs). Currently, there are limited established image analysis systems to specifically assess and quantify the sarcomeric organization of hPSC-derived cardiomyocytes (hPSC-CMs). Here, we report a fully automated and robust image analysis pipeline to detect z-lines and myofibrils from hPSC-CMs with a high-throughput live-imaging setup. Phenotype measurements were further quantified to evaluate the cardiotoxic effect of the anticancer drug Doxorubicin. Our findings show that this pipeline is able to capture z-lines and myofibrils. The pipeline filters out disrupted sarcomere structures and irrelevant noisy signals, which allows us to perform automated high-throughput imaging for accurate quantification of cardiomyocyte injury.

Authors 6

1. Lu Cao corresponding Aachen Imaging and Bioinformatics Group Leiden Institute of Advanced Computer Science

   Leiden University

   Affiliation as printed

   Imaging and Bioinformatics Group, Leiden Institute of Advanced Computer Science (LIACS), Leiden University , Leiden 2333 CA , The Netherlands

2. Linde Schoenmaker Aachen Division of Drug Discovery and Safety Leiden Academic Centre for Drug Research

   Leiden University

   Affiliation as printed

   Division of Drug Discovery and Safety, Leiden Academic Centre for Drug Research, Leiden University , Leiden 2333 CC , The Netherlands

3. Simone A. ten Den

   University of Twente

   Affiliation as printed

   Applied Stem Cell Technologies, TechMed Centre, University of Twente , Enschede 7522 NB , The Netherlands

4. Robert C. J. J. Passier Aachen Department of Anatomy and Embryology

   Leiden University · University of Twente · Leiden University Medical Center

   Affiliation as printed

   Applied Stem Cell Technologies, TechMed Centre, University of Twente , Enschede 7522 NB , The Netherlands

   Department of Anatomy and Embryology, Leiden University Medical Centre , Leiden 2300 RC , The Netherlands

5. Verena Schwach

   University of Twente

   Affiliation as printed

   Applied Stem Cell Technologies, TechMed Centre, University of Twente , Enschede 7522 NB , The Netherlands

6. Fons J. Verbeek Aachen Imaging and Bioinformatics Group Leiden Institute of Advanced Computer Science

   Leiden University

   Affiliation as printed

   Imaging and Bioinformatics Group, Leiden Institute of Advanced Computer Science (LIACS), Leiden University , Leiden 2333 CA , The Netherlands