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

Autor: Corrado Poggesi, Chiara Tesi, Sara Landi, Cecilia Ferrantini, Camilla Parmeggiani, Marianna Langione, Bruno Grandinetti, Michael Regnier, Chiara Palandri, Laura Sartiani, Josè Manuel Pioner, Patrizia Benzoni, Andrea Barbuti, Flavia Lupi, David L. Mack, Raffaele Coppini, Luca Boarino, Daniele Martella, Elisabetta Cerbai, Federico Ferrarese Lupi, Valentina Balducci, Silvia Querceto, Lorenzo Santini
Rok vydání: 2019
Předmět:
0301 basic medicine
Inotrope
Cardiomyopathy
Action Potentials
cardiomyocytes
Stimulation
030204 cardiovascular system & hematology
Substrate Specificity
lcsh:Chemistry
action potential
0302 clinical medicine
Biomimetics
Myocytes
Cardiac
lcsh:QH301-705.5
Cells
Cultured
Excitation Contraction Coupling
Spectroscopy
Chemistry
Cell Differentiation
Hydrogels
General Medicine
3. Good health
Computer Science Applications
Cell biology
Sarcoplasmic Reticulum
fluorescence
Cardiomyopathies
Calcium handling
Adrenergic beta-Antagonists
Induced Pluripotent Stem Cells
chemistry.chemical_element
Calcium
Article
Catalysis
Inorganic Chemistry
03 medical and health sciences
Action potential
Cardiomyocytes
Fluorescence
Human induced pluripotent stem cells
Long-term culture
Maturation
medicine
Humans
Physical and Theoretical Chemistry
Molecular Biology
maturation
Endoplasmic reticulum
Organic Chemistry
medicine.disease
human induced pluripotent stem cells
long-term culture
Electrophysiology
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
calcium handling
Function (biology)
Zdroj: International Journal of Molecular Sciences
International journal of molecular sciences
20 (2019): 3799–3799. doi:10.3390/ijms20153799
info:cnr-pdr/source/autori:Pioner, Jose Manuel; Santini, Lorenzo; Palandri, Chiara; Martella, Daniele; Lupi, Flavia; Langione, Marianna; Querceto, Silvia; Grandinetti, Bruno; Balducci, Valentina; Benzoni, Patrizia; Landi, Sara; Barbuti, Andrea; Lupi, Federico Ferrarese; Boarino, Luca; Sartiani, Laura; Tesi, Chiara; Mack, David L.; Regnier, Michael; Cerbai, Elisabetta; Parmeggiani, Camilla; Poggesi, Corrado; Ferrantini, Cecilia; Coppini, Raffaele/titolo:Optical Investigation of Action Potential and Calcium Handling Maturation of hiPSC-Cardiomyocytes on Biomimetic Substrates/doi:10.3390%2Fijms20153799/rivista:International journal of molecular sciences (Print)/anno:2019/pagina_da:3799/pagina_a:3799/intervallo_pagine:3799–3799/volume:20
International Journal of Molecular Sciences, Vol 20, Iss 15, p 3799 (2019)
Volume 20
Issue 15
ISSN: 1422-0067
DOI: 10.3390/ijms20153799
Popis: 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 &beta
adrenergic stimulation are time-dependent events underlying excitation contraction coupling (ECC) maturation of hiPSC-CM
biomimetic substrates can promote calcium-handling regulation towards adult-like kinetics. Simultaneous optical recordings of long-term cultured hiPSC-CMs on biomimetic substrates favor high-throughput electrophysiological analysis aimed at testing (mechanistic hypothesis on) disease progression and pharmacological interventions in patient-derived hiPSC-CMs.
Databáze: OpenAIRE
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