@article{MayerArrizabalagaLiebetal.2018, author = {Mayer, Margot and Arrizabalaga, Onetsine and Lieb, Florian and Ciba, Manuel and Ritter, Sylvia and Thielemann, Christiane}, title = {Electrophysiological investigation of human embryonic stem cell derived neurospheres using a novel spike detection algorithm}, series = {Biosensors and Bioelectronics}, volume = {2018}, journal = {Biosensors and Bioelectronics}, number = {100}, doi = {10.1016/j.bios.2017.09.034}, pages = {462 -- 468}, year = {2018}, abstract = {Microelectrode array (MEA) technology in combination with three-dimensional (3D) neuronal cell models derived from human embryonic stem cells (hESC) provide an excellent tool for neurotoxicity screening. Yet, there are significant challenges in terms of data processing and analysis, since neuronal signals have very small amplitudes and the 3D structure enhances the level of background noise. Thus, neuronal signal analysis requires the application of highly sophisticated algorithms. In this study, we present a new approach optimized for the detection of spikes recorded from 3D neurospheres (NS) with a very low signal-to-noise ratio. This was achieved by extending simple threshold-based spike detection utilizing a highly sensitive algorithm named SWTTEO. This analysis procedure was applied to data obtained from hESC-derived NS grown on MEA chips. Specifically, we examined changes in the activity pattern occurring within the first ten days of electrical activity. We further analyzed the response of NS to the GABA receptor antagonist bicuculline. With this new algorithm method we obtained more reliable results compared to the simple threshold-based spike detection.}, subject = {Embryonale Stammzelle}, language = {en} } @inproceedings{MayerArrizabalagaSchroederetal.2018, author = {Mayer, Margot and Arrizabalaga, Onetsine and Schr{\"o}der, Insa and Ritter, Sylvia and Thielemann, Christiane}, title = {Human Embryonic Stem Cell Derived Neurospheres - 2D and 3D Cell Culture in one sample}, year = {2018}, abstract = {Various studies have shown that two dimensional (2D) neuronal cell cultures does not recapitulate structure and physiology of three-dimensional (3D) in vivo tissues. These findings are of paramount importance for drug screening, since the response to neurotoxicological substances may differ for 2D und 3D cell culture models. To address this topic, we present human embryonic stem cell (hESC) derived neurospheres (NS) coupled onto microelectrode array (MEA) chips as a model system that includes a 3D NS as well as an outgrowing 2D monolayer allowing direct comparison of functionality within one culture. Preliminary results revealed an enhanced functional reactions of 3D NS to GABA receptor antagonist bicuculline compared to the 2D domain. Thus we have the first evidence that hESC derived NS are a promising model system for neurotoxicity testing enabling a direct comparison between functionality of neurons grown in 2D or 3D.}, subject = {Embryonale Stammzelle}, language = {en} } @inproceedings{MayerArrizabalagaRitteretal.2016, author = {Mayer, Margot and Arrizabalaga, Onetsine and Ritter, Sylvia and Thielemann, Christiane}, title = {Human Embryonic Stem Cell Derived Neurospheres - A Novel Three Dimensional Model For Neurotoxicological Studies}, series = {Frontiers}, volume = {2016}, booktitle = {Frontiers}, number = {MEA Meeting 2016}, doi = {10.3389/conf.fnins.2016.93.00081}, year = {2016}, abstract = {At present, most neurotoxicological studies in the field of microelectrode array (MEA) technology are based on in vivo or in vitro animal models, particularly in mice or rats. These models contributed much to our knowledge about molecular and cellular mechanisms of neurotoxins affecting the central nervous system. Yet, animal models are not necessarily capable to forecasting the effectiveness of treatment in clinical trials. Therefore the development and characterization of suitable neuronal cell models derived from human cells is emerging in the field of toxicity testing. In this study, we present neurospheres (NS) as a new three dimensional (3D) neuronal cell model based on human embryonic stem cells (hESC), coupled onto microelectrode arrays (MEA). This cell-based assay serves as platform to investigate effects of neuroactive substances on network communication. In order to characterize the neurospheres' reaction, the well-known GABA receptor antagonist bicuculline and the sodium channel blocker carbamazepine are applied. Preliminary results reveal anticipated and physiologically reasonable alterations in network activity. Thus, we have the first evidence that hESC derived NS are a promising 3D cell model for neurotoxicity testing. In further studies, this model will be used to investigate effects of ionizing radiation on network signaling.}, subject = {Mikroelektrode}, language = {en} } @techreport{MayerArrizabalagaRitteretal.2015, author = {Mayer, Margot and Arrizabalaga, Onetsine and Ritter, Sylvia and Thielemann, Christiane}, title = {Human embryonic stem cell derived neurospheres form functional networks on microelectrode arrays}, series = {GSI Scientific Report 2015}, volume = {2015}, journal = {GSI Scientific Report 2015}, number = {GSI Report 2016-1}, doi = {10.15120/GR-2016-1}, pages = {205 -- 205}, year = {2015}, subject = {Embryonale Stammzelle}, language = {en} }