Refine
Institute
Language
- English (8)
Document Type
- Conference Proceeding (8) (remove)
Is part of the Bibliography
- no (8)
Electromechanical model of hiPSC-derived ventricular cardiomyocytes cocultured with fibroblasts
(2018)
The CellDrum provides an experimental setup to study the mechanical effects of fibroblasts co-cultured with hiPSC-derived ventricular cardiomyocytes. Multi-scale computational models based on the Finite Element Method are developed. Coupled electrical cardiomyocyte-fibroblast models (cell level) are embedded into reaction-diffusion equations (tissue level) which compute the propagation of the action potential in the cardiac tissue. Electromechanical coupling is realised by an excitation-contraction model (cell level) and the active stress arising during contraction is added to the passive stress in the force balance, which determines the tissue displacement (tissue level). Tissue parameters in the model can be identified experimentally to the specific sample.
The discovery of human induced pluripotent stem cells reprogrammed from somatic cells [1] and their ability to differentiate into cardiomyocytes (hiPSC-CMs) has provided a robust platform for drug screening [2]. Drug screenings are essential in the development of new components, particularly for evaluating the potential of drugs to induce life-threatening pro-arrhythmias. Between 1988 and 2009, 14 drugs have been removed from the market for this reason [3]. The microelectrode array (MEA) technique is a robust tool for drug screening as it detects the field potentials (FPs) for the entire cell culture. Furthermore, the propagation of the field potential can be examined on an electrode basis. To analyze MEA measurements in detail, we have developed an open-source tool.
Human induced pluripotent stem cells (hiPSCs) have shown to be promising in disease studies and drug screenings [1]. Cardiomyocytes derived from hiPSCs have been extensively investigated using patch-clamping and optical methods to compare their electromechanical behaviour relative to fully matured adult cells. Mathematical models can be used for translating findings on hiPSCCMs to adult cells [2] or to better understand the mechanisms of various ion channels when a drug is applied [3,4]. Paci et al. (2013) [3] developed the first model of hiPSC-CMs, which they later refined based on new data [3]. The model is based on iCells® (Fujifilm Cellular Dynamics, Inc. (FCDI), Madison WI, USA) but major differences among several cell lines and even within a single cell line have been found and motivate an approach for creating sample-specific models. We have developed an optimisation algorithm that parameterises the conductances (in S/F=Siemens/Farad) of the latest Paci et al. model (2018) [5] using current-voltage data obtained in individual patch-clamp experiments derived from an automated patch clamp system (Patchliner, Nanion Technologies GmbH, Munich).
As part of the transnational research project EDITOR, a parabolic trough collector system (PTC) with concrete thermal energy storage (C-TES) was installed and commissioned in Limassol, Cyprus. The system is located on the premises of the beverage manufacturer KEAN Soft Drinks Ltd. and its function is to supply process steam for the factory's pasteurisation process [1]. Depending on the factory's seasonally varying capacity for beverage production, the solar system delivers between 5 and 25 % of the total steam demand. In combination with the C-TES, the solar plant can supply process steam on demand before sunrise or after sunset. Furthermore, the C-TES compensates the PTC during the day in fluctuating weather conditions. The parabolic trough collector as well as the control and oil handling unit is designed and manufactured by Protarget AG, Germany. The C-TES is designed and produced by CADE Soluciones de Ingeniería, S.L., Spain. In the focus of this paper is the description of the operational experience with the PTC, C-TES and boiler during the commissioning and operation phase. Additionally, innovative optimisation measures are presented.