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棒状微图案增强了源自人诱导多能干细胞的心肌细胞的电生理成熟。

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

机构信息

Université de Paris Cité, PARCC, INSERM, 75006 Paris, France.

INSERM UMR_S 1219, Bordeaux Population Health Research Center, University of Bordeaux, Bordeaux, France.

出版信息

Stem Cell Reports. 2024 Oct 8;19(10):1417-1431. doi: 10.1016/j.stemcr.2024.08.005. Epub 2024 Sep 19.

DOI:10.1016/j.stemcr.2024.08.005
PMID:39303707
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11561463/
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.

摘要

人诱导多能干细胞衍生的心肌细胞（hiPSC-CMs）在药物筛选和疾病建模方面具有巨大的潜力。然而，与成人心肌细胞相比，hiPSC-CMs 仍然不成熟。从成人心脏中分离出来的心肌细胞具有典型的杆状形态。在这里，我们试图开发一种简单的方法，通过使用由重复的矩形（长 120μm×宽 30μm）组成的杆状细胞微图案化基质来改善 hiPSC-CMs 的结构成熟度，该基质被化学细胞排斥物包围。生成的 hiPSC-CMs 表现出许多类似于成人心肌细胞的特征，包括伸长的细胞形状、组织良好的肌节和增加的肌原纤维密度。结构特性的改善与晚期心室动作电位的富集相关，其特征是更超极化的静息膜电位和增强的去极化，这与钠电流密度的增加一致。通过这种方法生成的更成熟的 hiPSC-CMs 可以作为一种有用的体外平台，用于表征心血管疾病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61c0/11561463/0fadbf8960c3/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61c0/11561463/6ca30f8edc9d/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61c0/11561463/d718984dbbbc/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61c0/11561463/f6b891de0547/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61c0/11561463/107c8dbecf8f/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61c0/11561463/e3ba98ad4294/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61c0/11561463/0fadbf8960c3/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61c0/11561463/6ca30f8edc9d/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61c0/11561463/d718984dbbbc/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61c0/11561463/f6b891de0547/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61c0/11561463/107c8dbecf8f/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61c0/11561463/e3ba98ad4294/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61c0/11561463/0fadbf8960c3/gr5.jpg

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本文引用的文献

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人诱导多能干细胞衍生心肌细胞中钙处理的成熟及对底物硬度增加的适应性：全长肌营养不良蛋白缺乏的影响
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Enhancing iPSC-CM Maturation Using a Matrigel-Coated Micropatterned PDMS Substrate.使用 Matrigel 涂覆的微图案化 PDMS 基底增强 iPSC-CM 成熟。
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