Journal
STEM CELL REPORTS
Volume 6, Issue 6, Pages 885-896Publisher
CELL PRESS
DOI: 10.1016/j.stemcr.2016.04.006
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Funding
- University of Siena, Italy
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Heart and Stroke Foundation of Canada Postdoctoral Fellowship
- NIH [P30 EY01730, HL111197, HD048895, U01 HL100405, P01 GM081619, R01 HL084642, P01 HL094374]
- Fondation Leducq Transatlantic Network of Excellence
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Tension production and contractile properties are poorly characterized aspects of excitation-contraction coupling of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Previous approaches have been limited due to the small size and structural immaturity of early-stage hiPSC-CMs. We developed a substrate nanopatterning approach to produce hiPSC-CMs in culture with adult-like dimensions, T-tubule-like structures, and aligned myofibrils. We then isolated myofibrils from hiPSC-CMs and measured the tension and kinetics of activation and relaxation using a custom-built apparatus with fast solution switching. The contractile properties and ultrastructure of myofibrils more closely resembled human fetal myofibrils of similar gestational age than adult preparations. We also demonstrated the ability to study the development of contractile dysfunction of myofibrils from a patient-derived hiPSC-CM cell line carrying the familial cardiomyopathy MYH7 mutation (E848G). These methods can bring new insights to understanding cardiomyocyte maturation and developmental mechanical dysfunction of hiPSC-CMs with cardiomyopathic mutations.
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