| Autor: |
Fitzwilliam Seibertz, Henry Sutanto, Rebekka Dülk, Julius Ryan D. Pronto, Robin Springer, Markus Rapedius, Aiste Liutkute, Melanie Ritter, Philipp Jung, Lea Stelzer, Luisa M. Hüsgen, Marie Klopp, Tony Rubio, Funsho E. Fakuade, Fleur E. Mason, Nico Hartmann, Steffen Pabel, Katrin Streckfuss-Bömeke, Lukas Cyganek, Samuel Sossalla, Jordi Heijman, Niels Voigt |
| Přispěvatelé: |
RS: Carim - H01 Clinical atrial fibrillation, Cardiologie, RS: Carim - H04 Arrhythmogenesis and cardiogenetics |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
Basic Research in Cardiology, 118(1):14. Springer |
| ISSN: |
0300-8428 |
| Popis: |
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 ICa,L density along with an increased ICa,L-triggered Ca2+-transient. INa and IK1 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 IK1 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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink