Journal
CIRCULATION RESEARCH
Volume 128, Issue 6, Pages 775-801Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCRESAHA.121.318183
Keywords
cardiac tissue; drug discovery; heart failure; humans; stem cells
Funding
- Netherlands Organ-on-Chip Initiative, an NWO Gravitation project - Ministry of Education, Culture and Science of the government of the Netherlands [024.003.001]
- European Union Horizon 2020 Research and Innovation Programme under the Marie Sklodowska Curie Actions [MSCA-IF 838985 SiGNATURE]
- Transnational Research Project on Cardiovascular Diseases [JTC2016_FP-40-021]
- Netherlands Organisation for Health Research and Development ZonMW (Meer Kennis met Minder Dieren [MKMD]) [114022504]
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Human pluripotent stem cells have the potential to differentiate into all cells of the body, but applications in cardiac research have been slower due to the complex 3-dimensional cues required for cardiomyocyte function. Recent tissue engineering approaches have addressed issues such as cardiomyocyte immaturity, leading to new possibilities in disease modeling, drug discovery, and heart repair through three-dimensional bioengineered heart tissues.
The ability of human pluripotent stem cells to form all cells of the body has provided many opportunities to study disease and produce cells that can be used for therapy in regenerative medicine. Even though beating cardiomyocytes were among the first cell types to be differentiated from human pluripotent stem cell, cardiac applications have advanced more slowly than those, for example, for the brain, eye, and pancreas. This is, in part, because simple 2-dimensional human pluripotent stem cell cardiomyocyte cultures appear to need crucial functional cues normally present in the 3-dimensional heart structure. Recent tissue engineering approaches combined with new insights into the dialogue between noncardiomyocytes and cardiomyocytes have addressed and provided solutions to issues such as cardiomyocyte immaturity and inability to recapitulate adult heart values for features like contraction force, electrophysiology, or metabolism. Three-dimensional bioengineered heart tissues are thus poised to contribute significantly to disease modeling, drug discovery, and safety pharmacology, as well as provide new modalities for heart repair. Here, we review the current status of 3-dimensional engineered heart tissues.
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