Network Activity Development in Cultured Cortical Neurons: Comparison Between Rat Embryonic and Human Pluripotent Stem Cell -Derived Systems
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1
University of Tampere, BioMediTech and Faculty of Medicine and Life Sciences, Finland
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2
Aarhus University, Department of Biomedicine, Denmark
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3
Aarhus University, Danish Research Institute of Translational Neuroscience - DANDRITE, Denmark
Microelectrode array (MEA) technology has been traditionally utilized for measurements of electrical activity from rodent brain tissue both in vivo and in vitro. While rodent MEA studies form the basis for the technology, also human MEA studies should be pushed forward to reassert MEA technology in fields such as disease modeling, neurotoxicology and drug discovery. There is still very limited amount of MEA publications describing neuronal networks derived from either human fetal or human pluripotent stem cell (hPSC) sources. Also, it should be noted that methods for hPSCs culture and neural differentiation have continuously developed and experienced significant improvements during recent years directly affecting neuronal functionality on MEA. These factors underline the need for critical comparison between hPSC-derived neural networks and their rodent counterparts. In the present study, hPSCs were differentiated to cortical neurons and their functional development was compared with primary rat cortical cultures (E17-E18). The hPSCs differentiated into mixed neural culture where development of neurons was followed by emergence of astrocytes after extended culture time. Neurons expressed markers for both upper and lower cortical layers and consisted mainly of glutamatergic and GABAergic subtypes. The activity in rat and human networks developed in similar timeframe reaching maximum spike rates already after three to four weeks of culture on MEA. Importantly, hPSC-derived neurons formed connective networks that reflect those described with rat cortical cultures. Network wide synchronous bursting behavior was evident in both rat and hPSC-derived cultures. While rat cortical cultures started deteriorating typically after five weeks in vitro, the hPSC-neurons sustained their synchronicity through the measurement period up to 100 days. Moreover, this network development was repeatable with several different hPSC lines proving robustness of the differentiation protocol. Despite many similarities between hPSC- and rat derived networks there are still distinct characteristics that need to be realized in data analysis and interpretation. However, achieving repeatedly synchronous network wide activity in hPSC-derived neuronal cultures demonstrates feasibility of these cells for applications such as in vitro modeling in order to discover human specific outcomes.
Keywords:
Pluripotent Stem Cells,
rat cortical cells,
Neurons,
neural networks,
synchronization
Conference:
MEA Meeting 2018 | 11th International Meeting on Substrate Integrated Microelectrode Arrays, Reutlingen, Germany, 4 Jul - 6 Jul, 2018.
Presentation Type:
Poster Presentation
Topic:
Stem cell-derived applications
Citation:
Hyvärinen
T,
Hyysalo
A,
Kapucu
E and
Narkilahti
S
(2019). Network Activity Development in Cultured Cortical Neurons: Comparison Between Rat Embryonic and Human Pluripotent Stem Cell -Derived Systems.
Conference Abstract:
MEA Meeting 2018 | 11th International Meeting on Substrate Integrated Microelectrode Arrays.
doi: 10.3389/conf.fncel.2018.38.00089
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Received:
14 Mar 2018;
Published Online:
17 Jan 2019.
*
Correspondence:
Mrs. Tanja Hyvärinen, University of Tampere, BioMediTech and Faculty of Medicine and Life Sciences, Tampere, Finland, tanja.hyvarinen@uta.fi