Characterization and application of electrically active neuronal networks established from human induced pluripotent stem cell-derived neural progenitor cells for neurotoxicity evaluation
| Autor: | Ulrike Hübenthal, Dagmar Wieczorek, Ellen Fritsche, Farina Bendt, James Adjaye, Stefan Masjosthusmann, Julia Hartmann, Stephan Theiss, Gabriele Brockerhoff, Julia Tigges, Barbara Hildebrandt, Karl Köhrer, Martin Schmuck, Laura Nimtz, Eike Keßel, Claudia Wigmann, Patrick Petzsch |
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| Rok vydání: | 2020 |
| Předmět: |
Neurotoxicology
0301 basic medicine Neuronal network Induced Pluripotent Stem Cells Action Potentials Biology Inhibitory postsynaptic potential 03 medical and health sciences Glutamatergic 0302 clinical medicine Neural Stem Cells Biological neural network medicine Animals Humans Induced pluripotent stem cell lcsh:QH301-705.5 Cells Cultured Neurons Stem cell MEA Neurotoxicity Cell Differentiation Cell Biology General Medicine medicine.disease Neural stem cell Rats 030104 developmental biology lcsh:Biology (General) GABAergic hiPSC-NPC Electrical activity Neuroscience 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Stem Cell Research, Vol 45, Iss, Pp-(2020) |
| ISSN: | 1873-5061 |
| DOI: | 10.1016/j.scr.2020.101761 |
| Popis: | Neurotoxicity is mediated by a variety of modes-of-actions leading to disturbance of neuronal function. In order to screen larger numbers of compounds for their neurotoxic potential, in vitro functional neuronal networks (NN) might be helpful tools. We established and characterized human NN (hNN) from hiPSC-derived neural progenitor cells by comparing hNN formation with two different differentiation media: in presence (CINDA) and absence (neural differentiation medium (NDM)) of maturation-supporting factors. As a NN control we included differentiating rat NN (rNN) in the study. Gene/protein expression and electrical activity from in vitro developing NN were assessed at multiple time points. Transcriptomes of 5, 14 and 28 days in vitro CINDA-grown hNN were compared to gene expression profiles of in vivo human developing brains. Molecular expression analyses as well as measures of electrical activity indicate that NN mature into neurons of different subtypes and astrocytes over time. In contrast to rNN, hNN are less electrically active within the same period of differentiation time, yet hNN grown in CINDA medium develop higher firing rates than hNN without supplements. Challenge of NN with neuronal receptor stimulators and inhibitors demonstrate presence of inhibitory, GABAergic neurons, whereas glutamatergic responses are limited. hiPSC-derived GABAergic hNN grown in CINDA medium might be a useful tool as part of an in vitro battery for assessing neurotoxicity. |
| Databáze: | OpenAIRE |
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