TY - CHAP A1 - Ritter, Sylvia A1 - Durante, Marco A1 - Helm, Alexander A1 - Steger, Frederik A1 - Daus, Andreas A1 - Frieß, Johannes T1 - Assessment of cardiotoxicity of heavy ions in vitro: generation and electrophysiology of cardiomyocytes T2 - 39th COSPAR Scientific Assembly, Mysore, India KW - Herzmuskelzelle KW - Kardiotoxizität Y1 - 2014 ER - TY - JOUR A1 - Mayer, Margot A1 - Arrizabalaga, Onetsine A1 - Lieb, Florian A1 - Ciba, Manuel A1 - Ritter, Sylvia A1 - Thielemann, Christiane T1 - Electrophysiological investigation of human embryonic stem cell derived neurospheres using a novel spike detection algorithm JF - Biosensors and Bioelectronics N2 - 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. KW - Microelectrode array KW - Neurosphere KW - Spike detection algorithm KW - Human embryonic stem cell-derived neurons KW - SWTTEO KW - Embryonale Stammzelle Y1 - 2018 U6 - https://doi.org/10.1016/j.bios.2017.09.034 VL - 2018 IS - 100 SP - 462 EP - 468 ER - TY - CHAP A1 - Mayer, Margot A1 - Arrizabalaga, Onetsine A1 - Schröder, Insa A1 - Ritter, Sylvia A1 - Thielemann, Christiane T1 - Human Embryonic Stem Cell Derived Neurospheres – 2D and 3D Cell Culture in one sample N2 - 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. KW - MEA Chips KW - neurospheres KW - human embryonic stem cells KW - 3D KW - Bicuculline KW - Embryonale Stammzelle Y1 - 2018 UR - https://www.frontiersin.org/10.3389/conf.fncel.2018.38.00078/event_abstract ER - TY - JOUR A1 - Heselich, Anja A1 - Frieß, Johannes A1 - Ritter, Sylvia A1 - Benz, Naja A1 - Layer, Paul A1 - Thielemann, Christiane T1 - High LET radiation shows no major cellular and functional effects on primary cardiomyocytes in vitro JF - Life Sciences in Space Research N2 - It is well known that ionizing radiation causes adverse effects on various mammalian tissues. However, there is little information on the biological effects of heavy ion radiation on the heart. In order to fill this gap, we systematically examined DNA-damage induction and repair, as well as proliferation and apoptosis in avian cardiomyocyte cultures irradiated with heavy ions such as titanium and iron, relevant for manned space-flight, and carbon ions, as used for radiotherapy. Further, and to our knowledge for the first time, we analyzed the effect of heavy ion radiation on the electrophysiology of primary cardiomyocytes derived from chicken embryos using the non-invasive microelectrode array (MEA) technology. As electrophysiological endpoints beat rate and field action potential duration were analyzed. The cultures clearly exhibited the capacity to repair induced DNA damage almost completely within 24 h, even at doses of 7 Gy, and almost completely recovered from radiation-induced changes in proliferative behavior. Interestingly, no significant effects on apoptosis could be detected. Especially the functionality of primary cardiac cells exhibited a surprisingly high robustness against heavy ion radiation, even at doses of up to 7 Gy. In contrast to our previous study with X-rays the beat rate remained more or less unaffected after heavy ion radiation, independently of beam quality. The only change we could observe was an increase of the field action potential duration of up to 30% after titanium irradiation, diminishing within the following three days. This potentially pathological observation may be an indication that heavy ion irradiation at high doses could bear a long-term risk for cardiovascular disease induction. KW - Cardiomyocytes KW - Heavy ion irradiation KW - Space radiation KW - Electrophysiology KW - MEA-technology KW - Zellkultur KW - Herzmuskelzelle Y1 - 2018 U6 - https://doi.org/10.1016/j.lssr.2018.01.001 VL - 2018 IS - 16 SP - 93 EP - 100 ER - TY - CHAP A1 - Mayer, Margot A1 - Arrizabalaga, Onetsine A1 - Ritter, Sylvia A1 - Thielemann, Christiane T1 - Human Embryonic Stem Cell Derived Neurospheres - A Novel Three Dimensional Model For Neurotoxicological Studies T2 - Frontiers N2 - 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. KW - human embryonic stem cells KW - neurospheres KW - MEA chips KW - 3D KW - Mikroelektrode KW - Array KW - Embryonale Stammzelle Y1 - 2016 U6 - https://doi.org/10.3389/conf.fnins.2016.93.00081 VL - 2016 IS - MEA Meeting 2016 ER - TY - RPRT A1 - Mayer, Margot A1 - Müller, Benedikt A1 - Kadereit, Suzanne A1 - Ritter, Sylvia A1 - Thielemann, Christiane T1 - Human neurospheres on microelectrode arrays: a model to investigate ionizing radiation effects on neuronal network communication T2 - GSI SCIENTIFIC REPORT 2014 KW - Neuronales Netz KW - Mikroelektrode KW - Array KW - Ionisierende Strahlung Y1 - 2014 U6 - https://doi.org/10.15120/GR-2015-1-APPA-HEALTH-15 ER - TY - RPRT A1 - Materna, Miriam A1 - Helm, Alexander A1 - Hessel, Petra A1 - Frieß, Johannes A1 - Thielemann, Christiane A1 - Pignalosa, Diana A1 - Mäntele, Werner A1 - Durante, Marco A1 - Ritter, Sylvia T1 - First electrophysiological studies on mouse embryonic stem cell-derived cardiomyocytes KW - Herzmuskelzelle KW - Elektrophysiologie Y1 - 2012 ER - TY - CHAP A1 - Frieß, Johannes A1 - Ritter, Sylvia A1 - Daus, Andreas A1 - Layer, Paul A1 - Thielemann, Christiane A1 - Heselich, Anja T1 - Electrophysiologic and Molecular Characteristics of Cardiomyocytes after Heavy Ion Irradiation in the frame of the ESA IBER-10 Program T2 - Heavy Ion in Therapie and Space Radiation Symposium (HITSRS2013), 2013, Chiba, Japan KW - Herzmuskelzelle KW - Ionenbestrahlung KW - Schweres Ion Y1 - 2013 ER - TY - CHAP A1 - Steger, Frederik A1 - Frieß, Johannes A1 - Daus, Andreas A1 - Ritter, Sylvia A1 - Thielemann, Christiane T1 - Analysis of electrophysiological characteristics of cardiomyocytes following radiation exposure T2 - 8th International Meeting on Substrate-Integrated Microelectrode Arrays KW - Herzmuskelzelle KW - Strahlenbelastung Y1 - 2014 U6 - https://doi.org/10.13140/RG.2.1.4153.0400 SN - 2194-5519 SP - 153 ER - TY - CHAP A1 - Thielemann, Christiane A1 - Ritter, Sylvia A1 - Layer, Paul A1 - Frieß, Johannes A1 - Daus, Andreas A1 - Steger, Frederik A1 - Heselich, Anja T1 - Cellular effects of space radiation with relevance to cardiovascular diseases T2 - Life in Space for Life on Earth KW - Kardiovaskuläre Krankheit KW - Ionisierende Strahlung Y1 - 2014 N1 - IBER-10 SP - 560 ER -