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基于人诱导多能干细胞衍生的心肌细胞生成的 3D 环形心脏组织的多功能高通量测定法。

A versatile high-throughput assay based on 3D ring-shaped cardiac tissues generated from human induced pluripotent stem cell-derived cardiomyocytes.

机构信息

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

4Dcell, Montreuil, France.

出版信息

Elife. 2024 Apr 5;12:RP87739. doi: 10.7554/eLife.87739.

DOI:10.7554/eLife.87739
PMID:38578976
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11001295/
Abstract

We developed a 96-well plate assay which allows fast, reproducible, and high-throughput generation of 3D cardiac rings around a deformable optically transparent hydrogel (polyethylene glycol [PEG]) pillar of known stiffness. Human induced pluripotent stem cell-derived cardiomyocytes, mixed with normal human adult dermal fibroblasts in an optimized 3:1 ratio, self-organized to form ring-shaped cardiac constructs. Immunostaining showed that the fibroblasts form a basal layer in contact with the glass, stabilizing the muscular fiber above. Tissues started contracting around the pillar at D1 and their fractional shortening increased until D7, reaching a plateau at 25±1%, that was maintained up to 14 days. The average stress, calculated from the compaction of the central pillar during contractions, was 1.4±0.4 mN/mm. The cardiac constructs recapitulated expected inotropic responses to calcium and various drugs (isoproterenol, verapamil) as well as the arrhythmogenic effects of dofetilide. This versatile high-throughput assay allows multiple in situ mechanical and structural readouts.

摘要

我们开发了一种 96 孔板检测法，它能够快速、可重复且高通量地生成围绕着一个已知硬度的可变形的光学透明水凝胶（聚乙二醇[PEG]）支柱的 3D 心脏环。人类诱导多能干细胞衍生的心肌细胞与正常的成人真皮成纤维细胞以优化的 3:1 比例混合，自发组织成环形的心脏结构。免疫染色显示，成纤维细胞形成与玻璃接触的基底层，稳定上方的肌肉纤维。组织在第 1 天开始围绕支柱收缩，其缩短分数增加直到第 7 天，达到 25±1%的平台，直至 14 天仍保持不变。通过测量收缩过程中中心支柱的压缩，计算得到的平均应力为 1.4±0.4 mN/mm。这些心脏结构重现了对钙和各种药物（异丙肾上腺素、维拉帕米）的预期变力反应，以及多非利特的致心律失常作用。这种多功能的高通量检测法允许进行多种原位力学和结构检测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c27c/11001295/e79df3dfa96c/elife-87739-fig5.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c27c/11001295/53732c90a6ea/elife-87739-fig2-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c27c/11001295/8ecc46b4f7da/elife-87739-fig2-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c27c/11001295/5c469065b1fe/elife-87739-fig2-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c27c/11001295/f9f13133fc9c/elife-87739-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c27c/11001295/0c275ea89d34/elife-87739-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c27c/11001295/b994f944d30e/elife-87739-fig3-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c27c/11001295/5028e9c9faeb/elife-87739-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c27c/11001295/e79df3dfa96c/elife-87739-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c27c/11001295/9c6c459b9f27/elife-87739-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c27c/11001295/d02af0447f37/elife-87739-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c27c/11001295/27a345971625/elife-87739-fig1-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c27c/11001295/0e75592e6018/elife-87739-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c27c/11001295/53732c90a6ea/elife-87739-fig2-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c27c/11001295/8ecc46b4f7da/elife-87739-fig2-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c27c/11001295/5c469065b1fe/elife-87739-fig2-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c27c/11001295/f9f13133fc9c/elife-87739-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c27c/11001295/0c275ea89d34/elife-87739-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c27c/11001295/b994f944d30e/elife-87739-fig3-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c27c/11001295/5028e9c9faeb/elife-87739-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c27c/11001295/e79df3dfa96c/elife-87739-fig5.jpg

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2
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Nat Biomed Eng. 2022 Apr;6(4):327-338. doi: 10.1038/s41551-022-00885-3. Epub 2022 Apr 27.
3
Animal models and animal-free innovations for cardiovascular research: current status and routes to be explored. Consensus document of the ESC Working Group on Myocardial Function and the ESC Working Group on Cellular Biology of the Heart.
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PeerJ. 2024 Nov 27;12:e18422. doi: 10.7717/peerj.18422. eCollection 2024.
4
Rod-shaped micropatterning enhances the electrophysiological maturation of cardiomyocytes derived from human induced pluripotent stem cells.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。
Stem Cell Reports. 2024 Oct 8;19(10):1417-1431. doi: 10.1016/j.stemcr.2024.08.005. Epub 2024 Sep 19.
5
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JCI Insight. 2024 Jan 2;9(3):e161356. doi: 10.1172/jci.insight.161356.
动物模型和心血管研究的无动物创新：现状和探索途径。ESC 心肌功能工作组和 ESC 心脏细胞生物学工作组的共识文件。
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4
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