Cardiomyocytes from human pluripotent stem cells: From laboratory curiosity to industrial biomedical platform.
Cardiomyocytes from human pluripotent stem cells: From laboratory curiosity to industrial biomedical platform.
复制标题
人类多能干细胞的心肌细胞：从实验室好奇心到工业生物医学平台。
DOI：
10.1016/j.bbamcr.2015.10.014
复制
发表时间：
2016-07
期刊：
影响因子：
--
通讯作者：
Young LE
中科院分区：
文献类型：
--
作者：
Denning C;Borgdorff V;Crutchley J;Firth KS;George V;Kalra S;Kondrashov A;Hoang MD;Mosqueira D;Patel A;Prodanov L;Rajamohan D;Skarnes WC;Smith JG;Young LE
来自人类多能干细胞（hPSC-CM）的心肌细胞可以彻底改变生物医学。全球心力衰竭的负担将很快达到900亿美元，而意外的心脏毒性是28%的药物停药的原因。hPSC分离、Cas9/CRISPR基因组工程和hPSC-CM分化的进展改善了患者护理，使药物进入临床，并开启了安全药理学的新时代。然而，使用hPSC-CM的预测性心脏毒性从失败到几乎完全成功形成对比。由于这可能与细胞不成熟有关，因此正在努力使用生物化学和生物物理学线索来改善hPSC-CM的约30种结构和功能特性中的许多特性，使其接近成人CM中所见的那些特性。广泛应用hPSC-CM所需的其他发展包括亚型特异性、大规模分化的成本降低和表型瓶颈的消除。本综述将考虑hPSC-CM技术演变中的这些因素，以及它们与评估结构、线粒体功能、电生理学、钙瞬变和收缩性的高含量工业平台的整合。这篇文章是由Marcus Schaub和Hughes Abriel编辑的题为：心肌细胞生物学：心脏中发育和环境线索的整合的特刊的一部分。hPSC-CM药物筛选、疾病建模和Cas9/CRISPR工程成为常规。hPSC-CM用于改善患者治疗并协助将药物进展到临床。移植到心脏衰竭的猪和灵长类动物现在转化为人类。进展的障碍包括商品成本，亚型规范和成熟度。2D和3D hPSC-CM高含量表型分析平台发展迅速。
Cardiomyocytes from human pluripotent stem cells (hPSCs-CMs) could revolutionise biomedicine. Global burden of heart failure will soon reach USD $90bn, while unexpected cardiotoxicity underlies 28% of drug withdrawals. Advances in hPSC isolation, Cas9/CRISPR genome engineering and hPSC-CM differentiation have improved patient care, progressed drugs to clinic and opened a new era in safety pharmacology. Nevertheless, predictive cardiotoxicity using hPSC-CMs contrasts from failure to almost total success. Since this likely relates to cell immaturity, efforts are underway to use biochemical and biophysical cues to improve many of the ~ 30 structural and functional properties of hPSC-CMs towards those seen in adult CMs. Other developments needed for widespread hPSC-CM utility include subtype specification, cost reduction of large scale differentiation and elimination of the phenotyping bottleneck. This review will consider these factors in the evolution of hPSC-CM technologies, as well as their integration into high content industrial platforms that assess structure, mitochondrial function, electrophysiology, calcium transients and contractility. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel. hPSC-CM drug screening, disease modelling & Cas9/CRISPR engineering becoming routine. hPSC-CMs used to refine patient treatment & assist in progressing drugs to clinic. Transplantation into heart failure pigs and primates now translated to humans. Barriers to progression include cost of goods, subtype specification & maturation. 2D and 3D hPSC-CM high content phenotyping platforms evolving rapidly.