Rod-shaped micropatterning enhances the electrophysiological maturation of cardiomyocytes derived from human induced pluripotent stem cells.

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) offer great potential for drug screening and disease modeling. However, hiPSC-CMs remain immature compared to the adult cardiac cells. Cardiomyocytes isolated from adult human hearts have a typical rod-shaped morphology. Here, we sought to develop a simple method to improve the architectural maturity of hiPSC-CMs by using a rod-shaped cell micropatterned substrate consisting of repeated rectangles (120 μm long × 30 μm wide) surrounded by a chemical cell repellent. The generated hiPSC-CMs exhibit numerous characteristics similar to adult human cardiomyocytes, including elongated cell shape, well-organized sarcomeres, and increased myofibril density. The improvement in structural properties correlates with the enrichment of late ventricular action potentials characterized by a more hyperpolarized resting membrane potential and an enhanced depolarization consistent with an increased sodium current density. The more mature hiPSC-CMs generated by this method may serve as a useful in vitro platform for characterizing cardiovascular disease.

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Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests J.-S.H. reports research grants from Sanofi and Pliant Therapeutics unrelated to the present work and speaker, advisory board, or consultancy fees from Alnylam, Amgen, AstraZeneca, Bayer Pharma, BioSerenity, Boehringer Ingelheim, Bristol-Myers Squibb, Novartis, Novo Nordisk, and Vifor Pharma all unrelated to the present work. The rod-shaped cell micropatterned substrate is marketed by 4DCell (Montreuil, France).