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

IF 5.9 2区医学 Q1 CELL & TISSUE ENGINEERING Stem Cell Reports Pub Date : 2024-09-16 DOI:10.1016/j.stemcr.2024.08.005

Zeina R Al Sayed, Charlène Jouve, Magali Seguret, Andrea Ruiz-Velasco, Céline Pereira, David-Alexandre Trégouët, Jean-Sébastien Hulot

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Abstract

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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棒状微图案化可增强人类诱导多能干细胞心肌细胞的电生理成熟。

人类诱导多能干细胞衍生的心肌细胞（hiPSC-CMs）为药物筛选和疾病建模提供了巨大的潜力。然而，与成体心脏细胞相比，hiPSC-CMs 仍未成熟。从成人心脏分离的心肌细胞具有典型的杆状形态。在此，我们试图开发一种简单的方法，通过使用由重复矩形（长 120 μm × 宽 30 μm）组成的棒状细胞微图案基底，并用化学细胞驱避剂包围，来提高 hiPSC-CMs 的结构成熟度。生成的 hiPSC-CMs 表现出许多与成人人类心肌细胞相似的特征，包括细胞形状拉长、肌节组织良好和肌原纤维密度增加。结构特性的改善与心室晚期动作电位的丰富有关，其特点是静息膜电位更加超极化，去极化增强，与钠离子电流密度的增加一致。用这种方法生成的更成熟的 hiPSC-CMs 可作为表征心血管疾病的有用体外平台。

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来源期刊

Stem Cell Reports CELL & TISSUE ENGINEERING-CELL BIOLOGY

CiteScore

10.50

自引率

1.70%

发文量

200

审稿时长

28 weeks

期刊介绍： Stem Cell Reports publishes high-quality, peer-reviewed research presenting conceptual or practical advances across the breadth of stem cell research and its applications to medicine. Our particular focus on shorter, single-point articles, timely publication, strong editorial decision-making and scientific input by leaders in the field and a "scoop protection" mechanism are reasons to submit your best papers.