Optical Investigation of Action Potential and Calcium Handling Maturation of hiPSC-Cardiomyocytes on Biomimetic Substrates

International Journal of Molecular Sciences
Josè Manuel PionerRaffaele Coppini

Abstract

Cardiomyocytes from human induced pluripotent stem cells (hiPSC-CMs) are the most promising human source with preserved genetic background of healthy individuals or patients. This study aimed to establish a systematic procedure for exploring development of hiPSC-CM functional output to predict genetic cardiomyopathy outcomes and identify molecular targets for therapy. Biomimetic substrates with microtopography and physiological stiffness can overcome the immaturity of hiPSC-CM function. We have developed a custom-made apparatus for simultaneous optical measurements of hiPSC-CM action potential and calcium transients to correlate these parameters at specific time points (day 60, 75 and 90 post differentiation) and under inotropic interventions. In later-stages, single hiPSC-CMs revealed prolonged action potential duration, increased calcium transient amplitude and shorter duration that closely resembled those of human adult cardiomyocytes from fresh ventricular tissue of patients. Thus, the major contribution of sarcoplasmic reticulum and positive inotropic response to β-adrenergic stimulation are time-dependent events underlying excitation contraction coupling (ECC) maturation of hiPSC-CM; biomimetic substrates can promote calc...Continue Reading

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Citations

Dec 17, 2020·Journal of Cardiovascular Pharmacology·Michelangelo PaciJussi T Koivumäki
Sep 2, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Lorenzo SantiniRaffaele Coppini
May 7, 2021·Seminars in Cell & Developmental Biology·Sean A MurphyChulan Kwon
Sep 21, 2021·Frontiers in Physiology·Caterina CrediLeonardo Sacconi

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Methods Mentioned

BETA
enzymatic dissociation
scanning electron microscopy
chip
biopsies

Software Mentioned

hAdult
MetaMorph
CMs
Clampfit

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