Seibertz, Fitzwilliam and Sutanto, Henry and Duelk, Rebekka and Pronto, Julius Ryan D. and Springer, Robin and Rapedius, Markus and Liutkute, Aiste and Ritter, Melanie and Jung, Philipp and Stelzer, Lea and Huesgen, Luisa M. and Klopp, Marie and Rubio, Tony and Fakuade, Funsho E. and Mason, Fleur E. and Hartmann, Nico and Pabel, Steffen and Streckfuss-Boemeke, Katrin and Cyganek, Lukas and Sossalla, Samuel and Heijman, Jordi and Voigt, Niels (2023) Electrophysiological and calcium-handling development during long-term culture of human-induced pluripotent stem cell-derived cardiomyocytes. BASIC RESEARCH IN CARDIOLOGY, 118 (1): 14. ISSN 0300-8428, 1435-1803
Full text not available from this repository. (Request a copy)Abstract
Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are increasingly used for personalised medicine and preclinical cardiotoxicity testing. Reports on hiPSC-CM commonly describe heterogenous functional readouts and underdeveloped or immature phenotypical properties. Cost-effective, fully defined monolayer culture is approaching mainstream adoption; however, the optimal age at which to utilise hiPSC-CM is unknown. In this study, we identify, track and model the dynamic developmental behaviour of key ionic currents and Ca2+-handling properties in hiPSC-CM over long-term culture (30-80 days). hiPSC-CMs > 50 days post differentiation show significantly larger I-Ca,I-L density along with an increased I-Ca,I-L-triggered Ca2+-transient. I-Na and I-K1 densities significantly increase in late-stage cells, contributing to increased upstroke velocity and reduced action potential duration, respectively. Importantly, our in silico model of hiPSC-CM electrophysiological age dependence confirmed I-K1 as the key ionic determinant of action potential shortening in older cells. We have made this model available through an open source software interface that easily allows users to simulate hiPSC-CM electrophysiology and Ca2+-handling and select the appropriate age range for their parameter of interest. This tool, together with the insights from our comprehensive experimental characterisation, could be useful in future optimisation of the culture-to-characterisation pipeline in the field of hiPSC-CM research.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | RECTIFIER POTASSIUM CURRENT; INWARD RECTIFIER; SARCOPLASMIC-RETICULUM; CARDIAC REPOLARIZATION; SODIUM CURRENT; ATRIAL; CURRENTS; MATURATION; MYOCYTES; STIMULATION; Stem cell; Calcium handling; Maturation; Ion channel; Action potential; Cardiovascular |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 09 Apr 2024 06:59 |
| Last Modified: | 09 Apr 2024 06:59 |
| URI: | https://pred.uni-regensburg.de/id/eprint/60730 |
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