Miniaturized engineered heart tissues to study human cardiac functions
November 2023
Leiden University Medical Center (LUMC), Leiden, Netherlands
Human heart tissues grown as three-dimensional spheroids 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. Conventional EHTs, however, often require between 0.5 and 2 million cells, making large-scale screening of many EHTs costly. The goals of this study 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. It could be demonstrated that fully functional EHTs could be generated from physiologically relevant combinations of hiPSC-derived cardiomyocytes, cardiac fibroblasts and cardiac endothelial cells, using as few as 1.6 × 104 cells. The results showed that these EHTs were viable and functional up to 14 days after formation, and could be electrically paced in the frequency range between 0.6 and 3 Hz, with the optimum between 0.6 and 2 Hz. 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.
Miniaturized engineered heart tissues from hiPSC-derived triple cell type co-cultures to study human cardiac function
Berend J. van Meer
Added on: 05-13-2024
[1] https://www.sciencedirect.com/science/article/pii/S0006291X23010707?via%3Dihub
