Cardiomyocytes from human pluripotent stem cells: From laboratory curiosity to industrial biomedical platform.
Biochim Biophys Acta
; 1863(7 Pt B): 1728-48, 2016 Jul.
Article
in En
| MEDLINE
| ID: mdl-26524115
ABSTRACT
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.
Key words
Automated scalability; Calcium imaging; Cardiomyocytes; Cas9/CRISPR genome editing; Contractility; Disease modelling; Drug screening; Electrophysiology; Engineered heart tissue; High content platforms; Human embryonic stem cells; Human induced pluripotent stem cells; Maturation factors; Mitochondria; Muscular thin films
Full text:
1
Database:
MEDLINE
Main subject:
Cardiovascular Agents
/
Toxicity Tests
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Cell Lineage
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Myocytes, Cardiac
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Biomedical Research
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Drug Discovery
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Induced Pluripotent Stem Cells
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High-Throughput Screening Assays
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Heart Diseases
Type of study:
Etiology_studies
/
Prognostic_studies
Limits:
Humans
Language:
En
Year:
2016
Type:
Article