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人iPSC来源的心脏基质细胞可促进3D心脏微组织成熟
2020-05-28 18:21
来源：小柯机器人

荷兰莱顿大学医学中心Christine L. Mummery、Milena Bellin、Valeria V. Orlova等研究人员合作发现，人iPSC来源的心脏基质细胞能够促进3D心脏微组织的成熟，并揭示出非心肌细胞对心脏病的影响。该研究于2020年5月26日在线发表于《细胞—干细胞》。

研究人员表明，人诱导多能干细胞（hiPSC）来源的心肌细胞（CM）、心脏成纤维细胞（CF）和心脏内皮细胞的三细胞组合可增强三维显微组织（MT）的成熟度。具有CF的MT中的hiPSC-CM显示出T管的肌节结构改善、收缩力增强和线粒体呼吸，并且在电生理上比不含CFs的MT更成熟。介导成熟的相互作用包括hiPSC-CM和CF之间通过连接蛋白43（CX43）间隙连接和细胞内环状AMP（cAMP）的偶联。不同细胞系和分化细胞批次可高度重现数千个hiPSC-MT的大规模生产。
 
与含有健康对照hiPSC-CM的MT相比，来自致心律失常性心肌病患者的hiPSC-CF明显地概括了该疾病的特征。因此，这一MT模型是用于构建多细胞心脏病模型的简单通用平台，这将有助于行业和学术界进行高通量分子筛查。
 
据了解，来自人诱导多能干细胞（hiPSC）的心肌细胞（CM）在功能上不成熟，但是通过掺入工程组织或强制收缩可以改善这种情况。
 
附：英文原文

Title: Human-iPSC-Derived Cardiac Stromal Cells Enhance Maturation in 3D Cardiac Microtissues and Reveal Non-cardiomyocyte Contributions to Heart Disease

Author: Elisa Giacomelli, Viviana Meraviglia, Giulia Campostrini, Amy Cochrane, Xu Cao, Ruben W.J. van Helden, Ana Krotenberg Garcia, Maria Mircea, Sarantos Kostidis, Richard P. Davis, Berend J. van Meer, Carolina R. Jost, Abraham J. Koster, Hailiang Mei, David G. Míguez, Aat A. Mulder, Mario Ledesma-Terrón, Giulio Pompilio, Luca Sala, Daniela C.F. Salvatori, Roderick C. Slieker, Elena Sommariva, Antoine A.F. de Vries, Martin Giera, Stefan Semrau, Leon G.J. Tertoolen, Valeria V. Orlova, Milena Bellin, Christine L. Mummery

Issue&Volume: 2020-05-26

Abstract: Cardiomyocytes (CMs) from human induced pluripotent stem cells (hiPSCs) are functionally immature, but this is improved by incorporation into engineered tissues or forced contraction. Here, we showed that tri-cellular combinations of hiPSC-derived CMs, cardiac fibroblasts (CFs), and cardiac endothelial cells also enhance maturation in easily constructed, scaffold-free, three-dimensional microtissues (MTs). hiPSC-CMs in MTs with CFs showed improved sarcomeric structures with T-tubules, enhanced contractility, and mitochondrial respiration and were electrophysiologically more mature than MTs without CFs. Interactions mediating maturation included coupling between hiPSC-CMs and CFs through connexin 43 (CX43) gap junctions and increased intracellular cyclic AMP (cAMP). Scaled production of thousands of hiPSC-MTs was highly reproducible across lines and differentiated cell batches. MTs containing healthy-control hiPSC-CMs but hiPSC-CFs from patients with arrhythmogenic cardiomyopathy strikingly recapitulated features of the disease. Our MT model is thus a simple and versatile platform for modeling multicellular cardiac diseases that will facilitate industry and academic engagement in high-throughput molecular screening.

DOI: 10.1016/j.stem.2020.05.004

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30202-2

Cell Stem Cell：《细胞—干细胞》，创刊于2007年。隶属于细胞出版社，最新IF：25.269
官方网址：https://www.cell.com/cell-stem-cell/home
投稿链接：https://www.editorialmanager.com/cell-stem-cell/default.aspx


本期文章：《细胞—干细胞》：Online/在线发表

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