Miniaturized engineered heart tissues from hiPSC-derived triple cell type co-cultures to study human cardiac function

L. M. Windt, M. Wiendels, M. Dostanić, M. Bellin, P. M. Sarro, M. Mastrangeli, C. L. Mummery, B. J. van Meer*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

24 Downloads (Pure)

Abstract

Human heart tissues grown as three-dimensional spheroids and consisting of different cardiac cell types derived from pluripotent stem cells (hiPSCs) recapitulate aspects of human physiology better than standard two-dimensional models in vitro. They typically consist of less than 5000 cells and are used to measure contraction kinetics although not contraction force. By contrast, engineered heart tissues (EHTs) formed around two flexible pillars, can measure contraction force but conventional EHTs often require between 0.5 and 2 million cells. This makes large-scale screening of many EHTs costly. Our goals here were (i) to create a physiologically relevant model that required fewer cells than standard EHTs making them less expensive, and (ii) to ensure that this miniaturized model retained correct functionality. We demonstrated that fully functional EHTs could be generated from physiologically relevant combinations of hiPSC-derived cardiomyocytes (70%), cardiac fibroblasts (15%) and cardiac endothelial cells (15%), using as few as 1.6 × 104 cells. Our results showed that these EHTs were viable and functional up to 14 days after formation. The EHTs could be electrically paced in the frequency range between 0.6 and 3 Hz, with the optimum between 0.6 and 2 Hz. This was consistent across three downscaled EHT sizes tested. These findings suggest that miniaturized EHTs could represent a cost-effective microphysiological system for disease modelling and examining drug responses particularly in secondary screens for drug discovery.

Original languageEnglish
Pages (from-to)200-211
Number of pages12
JournalBiochemical and Biophysical Research Communications
Volume681
DOIs
Publication statusPublished - 2023

Keywords

  • Cardiac contraction
  • Cardiomyocytes
  • Engineered heart tissues
  • hiPSCs
  • Microphysiological system

Fingerprint

Dive into the research topics of 'Miniaturized engineered heart tissues from hiPSC-derived triple cell type co-cultures to study human cardiac function'. Together they form a unique fingerprint.

Cite this