Journal
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
Volume 138, Issue -, Pages 1-11Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.yjmcc.2019.10.001
Keywords
Induced pluripotent stem cells; 3D cardiac microtissues; Maturation; TDI; Electrophysiology; Contractile function
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Funding
- Maryland Stem Cell Research Fund [2016-MSCRFI-2735]
- Zegar Family Foundation
- Magic that Matters Fund
- NIH [S10OD-016374]
- Ministry of Science of Technology of Taiwan's Postdoctoral Research Abroad Program [105-2917-1-564-003-A1]
- American Heart Association fellowship [19POST34380424]
- Johns Hopkins Whiting School of Engineering
- Krieger School of Arts Sciences
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Recent advances in the understanding and use of pluripotent stem cells have produced major changes in approaches to the diagnosis and treatment of human disease. An obstacle to the use of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) for regenerative medicine, disease modeling and drug discovery is their immature state relative to adult myocardium. We show the effects of a combination of biochemical factors, thyroid hormone, dexamethasone, and insulin-like growth factor-1 (TDI) on the maturation of hiPSC-CMs in 3D cardiac microtissues (CMTs) that recapitulate aspects of the native myocardium. Based on a comparison of the gene expression profiles and the structural, ultrastructural, and electrophysiological properties of hiPSC-CMs in monolayers and CMTs, and measurements of the mechanical and pharmacological properties of CMTs, we find that TDI treatment in a 3D tissue context yields a higher fidelity adult cardiac phenotype, including sarcoplasmic reticulum function and contractile properties consistent with promotion of the maturation of hiPSC derived cardiomyocytes.
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