Electrophysiological- and Neuropharmacological-Based Benchmarking of Human Induced Pluripotent Stem Cell-Derived and Primary Rodent Neurons
Autor: | Willard J. Costain, Salma Alasmar, Umberto Banderali, Maria Ribecco-Lutkiewicz, Caroline Sodja, Marzia Martina, Slavisa Corluka, Amy Aylsworth, Anna Jezierski, Ewa Baumann, Joseph S. Tauskela |
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Rok vydání: | 2021 |
Předmět: |
Nervous system
Neurons education.field_of_study Population Induced Pluripotent Stem Cells Glutamate receptor Rodentia General Medicine Biology Inhibitory postsynaptic potential Electrophysiological Phenomena Rats Glutamatergic Electrophysiology Benchmarking medicine.anatomical_structure nervous system medicine Animals Humans Neuron Induced pluripotent stem cell education Neuroscience |
Zdroj: | Stem cell reviews and reports. 18(1) |
ISSN: | 2629-3277 |
Popis: | Human induced pluripotent stem cell (iPSC)-derived neurons are of interest for studying neurological disease mechanisms, developing potential therapies and deepening our understanding of the human nervous system. However, compared to an extensive history of practice with primary rodent neuron cultures, human iPSC-neurons still require more robust characterization of expression of neuronal receptors and ion channels and functional and predictive pharmacological responses. In this study, we differentiated human amniotic fluid-derived iPSCs into a mixed population of neurons (AF-iNs). Functional assessments were performed by evaluating electrophysiological (patch-clamp) properties and the effect of a panel of neuropharmacological agents on spontaneous activity (multi-electrode arrays; MEAs). These electrophysiological data were benchmarked relative to commercially sourced human iPSC-derived neurons (CNS.4U from Ncardia), primary human neurons (ScienCell™) and primary rodent cortical/hippocampal neurons. Patch-clamp whole-cell recordings showed that mature AF-iNs generated repetitive firing of action potentials in response to depolarizations, similar to that of primary rodent cortical/hippocampal neurons, with nearly half of the neurons displaying spontaneous post-synaptic currents. Immunochemical and MEA-based analyses indicated that AF-iNs were composed of functional glutamatergic excitatory and inhibitory GABAergic neurons. Principal component analysis of MEA data indicated that human AF-iN and rat neurons exhibited distinct pharmacological and electrophysiological properties. Collectively, this study establishes a necessary prerequisite for AF-iNs as a human neuron culture model suitable for pharmacological studies. |
Databáze: | OpenAIRE |
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