期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
卷 1863, 期 7, 页码 1728-1748出版社
ELSEVIER
DOI: 10.1016/j.bbamcr.2015.10.014
关键词
Human embryonic stem cells; Human induced pluripotent stem cells; Cas9/CRISPR genome editing; Cardiomyocytes; Drug screening; Disease modelling; Maturation factors; Muscular thin films; Engineered heart tissue; Automated scalability; High content platforms; Calcium imaging; Electrophysiology; Mitochondria; Contractility
资金
- BBSRC [BB/E006159/1, BB/G010390/1, BB/G021821/1] Funding Source: UKRI
- EPSRC [EP/H045384/1] Funding Source: UKRI
- MRC [G0801098, MR/L012618/1, G113/30, MR/M017354/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BBS/B/06164, BB/G021821/1, BB/G010390/1, BB/E006159/1] Funding Source: researchfish
- British Heart Foundation [RG/14/1/30588, PG/14/59/31000, RG/11/19/29264, PG/09/027/27141] Funding Source: researchfish
- Engineering and Physical Sciences Research Council [1229608, EP/H045384/1, 1379951, 1367509, 1118928] Funding Source: researchfish
- Heart Research UK [RG2616] Funding Source: researchfish
- Medical Research Council [MR/M017354/1, G113/30, MR/L012618/1, G0801098] Funding Source: researchfish
- National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) [NC/C013105/1, NC/K000225/1, NC/C013202/1] Funding Source: researchfish
- The British Council [04BX14CDLG] Funding Source: researchfish
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 similar to 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. (c) 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license
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