Journal
MATRIX BIOLOGY
Volume 85-86, Issue -, Pages 189-204Publisher
ELSEVIER
DOI: 10.1016/j.matbio.2019.04.001
Keywords
Cardiomyocytes; Tissue engineering; Electrophysiology; Electrical stimulation; Maturation; Microenvironment; Organ-on-a-chip; Heart
Categories
Funding
- Canadian Institutes of Health Research (CIHR) [MOP-126027, MOP-137107]
- Natural Sciences and Engineering Research Council of Canada (NSERC) [RGPIN 326982-10]
- NSERC-CIHR Collaborative Health Research Grant [CHRP 493737-16]
- National Institutes of Health [2R01 HL076485]
- NSERC Steacie Fellowship
- Canada Research Chair
- NSERC Post-graduate Fellowship
- NSERC CREATE Toep student award
- Ted Rogers Center for Heart Research Doctoral Award
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Organ-on-a-chip systems have the potential to revolutionize drug screening and disease modeling through the use of human stem cell-derived cardiomyocytes. The predictive power of these tissue models critically depends on the functional assembly and maturation of human cells that are used as building blocks for organon-a-chip systems. To resemble a more adult-like phenotype on these heart-on-a-chip systems, the surrounding micro-environment of individual cardiomyocyte needs to be controlled. Herein, we investigated the impact of four microenvironmental cues: cell seeding density, types and percentages of non-myocyte populations, the types of hydrogels used for tissue inoculation and the electrical conditioning regimes on the structural and functional assembly of human pluripotent stem cell-derived cardiac tissues. Utilizing a novel, plastic and open-access heart-on-a-chip system that is capable of continuous non-invasive monitoring of tissue contractions, we were able to study how different micro-environmental cues affect the assembly of the cardiomyocytes into a functional cardiac tissue. We have defined conditions that resulted in tissues exhibiting hallmarks of the mature human myocardium, such as positive force-frequency relationship and post-rest potentiation. (C) 2019 Elsevier B.V. All rights reserved.
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