Human perinatal stem cell derived extracellular matrix enables rapid maturation of hiPSC-CM structural and functional phenotypes.
Human perinatal stem cell derived extracellular matrix enables rapid maturation of hiPSC-CM structural and functional phenotypes.
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人类围产期干细胞来源的细胞外基质使HiPSC-CM的结构和功能表型迅速成熟。
DOI：
10.1038/s41598-020-76052-y
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发表时间：
2020-11-04
影响因子：
4.6
通讯作者：
Herron TJ
中科院分区：
文献类型：
--
作者：
Block T;Creech J;da Rocha AM;Marinkovic M;Ponce-Balbuena D;Jiménez-Vázquez EN;Griffey S;Herron TJ
人诱导多能干细胞衍生的心肌细胞（hiPSC-CM）的不成熟表型是将这些有价值的细胞用于临床前毒性测试和疾病建模的主要限制。在这里，我们测试了人围产期干细胞衍生的细胞外基质（ECM）比小鼠细胞衍生的ECM更大程度地促进hiPSC-CM成熟的假设。我们将人ECM称为Matrix Plus（Matrix Plus），并将其效果与市售小鼠ECM（Matrigel）进行比较。在Matrix Plus上培养的hiPSC-CM在冷冻保存解冻后7天在功能和结构上成熟。成熟的hiPSC-CM表现出杆状形态、高度组织化的肌节、升高的肌钙蛋白I表达以及线粒体分布和功能，与成年心肌细胞相似。Matrix Plus还促进成熟hiPSC-CM电生理功能，100%受试单层细胞对hERG离子通道特异性阻滞剂的反应为尖端扭转型室性心动过速（TdP）折返性心律失常激活。重要的是，Matrix Plus能够使用成熟的人类心肌细胞进行高通量心脏毒性筛选，并利用健康与环境科学研究所（HESI）协调的不断发展的综合体外致心律失常试验（CiPA）推荐的参比化合物进行验证。Matrix Plus为hiPSC-CM不成熟的常见问题提供了解决方案，该问题阻碍了这些基于人的细胞测定用于临床前药物发现的实施。
The immature phenotype of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) is a major limitation to the use of these valuable cells for pre-clinical toxicity testing and for disease modeling. Here we tested the hypothesis that human perinatal stem cell derived extracellular matrix (ECM) promotes hiPSC-CM maturation to a greater extent than mouse cell derived ECM. We refer to the human ECM as Matrix Plus (Matrix Plus) and compare effects to commercially available mouse ECM (Matrigel). hiPSC-CMs cultured on Matrix Plus mature functionally and structurally seven days after thaw from cryopreservation. Mature hiPSC-CMs showed rod-shaped morphology, highly organized sarcomeres, elevated cTnI expression and mitochondrial distribution and function like adult cardiomyocytes. Matrix Plus also promoted mature hiPSC-CM electrophysiological function and monolayers’ response to hERG ion channel specific blocker was Torsades de Pointes (TdP) reentrant arrhythmia activations in 100% of tested monolayers. Importantly, Matrix Plus enabled high throughput cardiotoxicity screening using mature human cardiomyocytes with validation utilizing reference compounds recommended for the evolving Comprehensive In Vitro Proarrhythmia Assay (CiPA) coordinated by the Health and Environmental Sciences Institute (HESI). Matrix Plus offers a solution to the commonly encountered problem of hiPSC-CM immaturity that has hindered implementation of these human based cell assays for pre-clinical drug discovery.
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影响因子：
20.1
作者：
Feaster TK;Cadar AG;Wang L;Williams CH;Chun YW;Hempel JE;Bloodworth N;Merryman WD;Lim CC;Wu JC;Knollmann BC;Hong CC
通讯作者：
Hong CC
影响因子：
48
作者：
Burridge, Paul W.;Matsa, Elena;Shukla, Praveen;Lin, Ziliang C.;Churko, Jared M.;Ebert, Antje D.;Lan, Feng;Diecke, Sebastian;Huber, Bruno;Mordwinkin, Nicholas M.;Plews, Jordan R.;Abilez, Oscar J.;Cui, Bianxiao;Gold, Joseph D.;Wu, Joseph C.
通讯作者：
Wu, Joseph C.
DOI：
10.1016/j.matbio.2016.01.004
发表时间：
2016-05
期刊：
Matrix biology : journal of the International Society for Matrix Biology
影响因子：
--
作者：
Marinkovic M;Block TJ;Rakian R;Li Q;Wang E;Reilly MA;Dean DD;Chen XD
通讯作者：
Chen XD
影响因子：
3.8
作者：
Andersen, Ditte C.;Kortesidis, Angela;Kassem, Moustapha
通讯作者：
Kassem, Moustapha
影响因子：
1.2
作者：
Bizy, Alexandra;Guerrero-Serna, Guadalupe;Hu, Bin;Ponce-Balbuena, Daniela;Willis, B. Cicero;Zarzoso, Manuel;Ramirez, Rafael J.;Sener, Michelle F.;Mundada, Lakshmi V.;Klos, Matthew;Devaney, Eric J.;Vikstrom, Karen L.;Herron, Todd J.;Jalife, Jose
通讯作者：
Jalife, Jose