2. Academic Validation
  3. Industrialization of 3D hiPSC-cardiac microtissues for high-throughput cardiac safety and drug discovery screening

Industrialization of 3D hiPSC-cardiac microtissues for high-throughput cardiac safety and drug discovery screening

  • Trends Biotechnol. 2025 Dec 18:S0167-7799(25)00490-1. doi: 10.1016/j.tibtech.2025.11.016.
Tessa de Korte 1,  Benjamin B Johnson 2,  Georgios Kosmidis 3,  Benoit Samson-Couterie 3,  Mervyn P H Mol 1,  Ruben W J van Helden 1,  Ehsan Razaghi 1,  Louise François 3,  Viviana Meraviglia 1,  Loukia Yiangou 1,  Tom Kuipers 4,  Hailiang Mei 4,  Milena Bellin 5,  Stefan R Braam 3,  Shushant Jain 3,  Christine L Mummery 2,  Richard P Davis 6
Affiliations

Affiliations

  • 1 Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands.
  • 2 Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands; The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden University Medical Center, Leiden, The Netherlands.
  • 3 Ncardia B.V., Leiden, The Netherlands.
  • 4 Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands.
  • 5 Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands; The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden University Medical Center, Leiden, The Netherlands; Department of Biology, University of Padova, Padova, Italy.
  • 6 Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands; The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden University Medical Center, Leiden, The Netherlands. Electronic address: r.p.davis@lumc.nl.
PMID: 41419348 DOI: 10.1016/j.tibtech.2025.11.016
Abstract

Current cardiac cell models for drug screening often face a trade-off between cellular maturity and throughput. 3D human-induced pluripotent stem cell (hiPSC)-based heart models typically exhibit adult-like features, but their use often requires large cell numbers or complex equipment. In this study, we developed cost-effective methods to scale the production of stem cell-derived cardiac microtissues (cMTs) containing three cardiac cell types and assess calcium transients and action potential metrics for high-throughput screening (HTS). Automating the procedure revealed reproducible drug responsiveness and predictive accuracy in a reference compound screen. Furthermore, an arrhythmic phenotype was reliably triggered in cMTs containing cardiomyocytes with an RYR2 mutation. Screening a library of more than 2000 compounds demonstrated the suitability of the assay for identifying potential antiarrhythmic agents. Our findings underscore the scalability of cMTs and their utility in disease modeling and HTS. The advanced technology readiness level of cMTs supports their regulatory uptake and acceptance within the pharmaceutical industry.

Keywords

3D cell models; automation; cardiac safety; cardiomyocytes; drug discovery; human pluripotent stem cells.

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