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

Autor: Windt LM; Department of Anatomy and Embryology, LUMC, Leiden, the Netherlands., Wiendels M; Department of Anatomy and Embryology, LUMC, Leiden, the Netherlands., Dostanić M; Department of Anatomy and Embryology, LUMC, Leiden, the Netherlands; Microelectronics, TU Delft, Delft, the Netherlands., Bellin M; Department of Anatomy and Embryology, LUMC, Leiden, the Netherlands; Department of Biology, University of Padua, Padua, Italy; Veneto Institute of Molecular Medicine, Padua, Italy., Sarro PM; Microelectronics, TU Delft, Delft, the Netherlands., Mastrangeli M; Microelectronics, TU Delft, Delft, the Netherlands., Mummery CL; Department of Anatomy and Embryology, LUMC, Leiden, the Netherlands., van Meer BJ; Department of Anatomy and Embryology, LUMC, Leiden, the Netherlands; Sync Biosystems, Leiden, the Netherlands. Electronic address: B.j.van_meer@lumc.nl.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2023 Nov 12; Vol. 681, pp. 200-211. Date of Electronic Publication: 2023 Sep 20.
DOI: 10.1016/j.bbrc.2023.09.034
Abstrakt: 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 × 10 4  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.
Competing Interests: Declaration of competing Interest CM is co-founder of Pluriomics (now Ncardia) and BM is co-founder and CTO of Demcon Biovitronix. The other authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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