Advances in Human Stem Cell-Derived Neuronal Cell Culturing and Analysis

Ylä‐Outinen, Laura; Tanskanen, Jarno M. A.; Kapucu, Fikret Emre; Hyysalo, Anu; Hyttinen, Jari; Narkilahti, Susanna

doi:10.1007/978-3-030-11135-9_13

Cited by 7 publications

(7 citation statements)

References 110 publications

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“…MEA electrodes record extracellular potentials of neurons or neuronal populations in the vicinity of the electrodes. MEA recordings can be analyzed to study, for example, spiking and bursting activity patterns and action potential waveforms across the whole MEA area or at a subset of electrodes [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

Astrocytes Exhibit a Protective Role in Neuronal Firing Patterns under Chemically Induced Seizures in Neuron–Astrocyte Co-Cultures

Ahtiainen

Genocchi

Tanskanen

et al. 2021

IJMS

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Astrocytes and neurons respond to each other by releasing transmitters, such as γ-aminobutyric acid (GABA) and glutamate, that modulate the synaptic transmission and electrochemical behavior of both cell types. Astrocytes also maintain neuronal homeostasis by clearing neurotransmitters from the extracellular space. These astrocytic actions are altered in diseases involving malfunction of neurons, e.g., in epilepsy, Alzheimer’s disease, and Parkinson’s disease. Convulsant drugs such as 4-aminopyridine (4-AP) and gabazine are commonly used to study epilepsy in vitro. In this study, we aim to assess the modulatory roles of astrocytes during epileptic-like conditions and in compensating drug-elicited hyperactivity. We plated rat cortical neurons and astrocytes with different ratios on microelectrode arrays, induced seizures with 4-AP and gabazine, and recorded the evoked neuronal activity. Our results indicated that astrocytes effectively counteracted the effect of 4-AP during stimulation. Gabazine, instead, induced neuronal hyperactivity and synchronicity in all cultures. Furthermore, our results showed that the response time to the drugs increased with an increasing number of astrocytes in the co-cultures. To the best of our knowledge, our study is the first that shows the critical modulatory role of astrocytes in 4-AP and gabazine-induced discharges and highlights the importance of considering different proportions of cells in the cultures.

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Section: Introductionmentioning

confidence: 99%

Astrocytes Exhibit a Protective Role in Neuronal Firing Patterns under Chemically Induced Seizures in Neuron–Astrocyte Co-Cultures

Ahtiainen

Genocchi

Tanskanen

et al. 2021

IJMS

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“…[ 37,94 ] As a functional readout besides calcium imaging, the electrophysiological analysis of in vitro neural network is often performed on MEAs. [ 30,95 ] However, the measurement of 3D models on MEAs is highly challenging, due to the planar structure of the electrodes and difficulties in positioning the cell‐containing material onto the electrodes Here, 3D bioprinting of hiPSC‐derived neural cells onto MEA electrodes might offer a valuable solution, especially for higher throughput applications. Although in this work we did not succeed in producing a ready‐to‐use 3D bioprinted neural model, we contribute to its generation by showing the printabilily and cytocompatibility of the developed ALG/GG/LAM gel blends.…”

Section: Discussionmentioning

confidence: 99%

“…[ 28 ] Ideally, extra‐cellular matrix (ECM)‐mimicking hydrogels should support cell survival, growth, differentiation, cell‐cell, and cell‐matrix adhesion, as well as facilitate proper nutrient flux. [ 29,30 ] In order to allow cellular outgrowth, a certain degree of hydrogel‐degradation is desirable. The material stiffness also plays an important role for the generation of neural models.…”

Section: Introductionmentioning

confidence: 99%

Human Induced Pluripotent Stem Cell‐Derived Neural Progenitor Cells Produce Distinct Neural 3D In Vitro Models Depending on Alginate/Gellan Gum/Laminin Hydrogel Blend Properties

Kapr

Petersilie

Distler

et al. 2021

Adv Healthcare Materials

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Stable and predictive neural cell culture models are a necessary premise for many research fields. However, conventional 2D models lack 3D cell‐material/‐cell interactions and hence do not reflect the complexity of the in vivo situation properly. Here two alginate/gellan gum/laminin (ALG/GG/LAM) hydrogel blends are presented for the fabrication of human induced pluripotent stem cell (hiPSC)‐based 3D neural models. For hydrogel embedding, hiPSC‐derived neural progenitor cells (hiNPCs) are used either directly or after 3D neural pre‐differentiation. It is shown that stiffness and stress relaxation of the gel blends, as well as the cell differentiation strategy influence 3D model development. The embedded hiNPCs differentiate into neurons and astrocytes within the gel blends and display spontaneous intracellular calcium signals. Two fit‐for‐purpose models valuable for i) applications requiring a high degree of complexity, but less throughput, such as disease modeling and long‐term exposure studies and ii) higher throughput applications, such as acute exposures or substance screenings are proposed. Due to their wide range of applications, adjustability, and printing capabilities, the ALG/GG/LAM based 3D neural models are of great potential for 3D neural modeling in the future.

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“…In vitro studies 194 are conducted using acute brain slices, retinas, and cultured neurons or cocultured neurons and astrocytes, organotypic cultures, 195 or organoids 196 (i.e., miniaturized and simplified organs in vitro ). Extracellular neuronal network function and characterization studies can be done using in vitro MEAs, 49 , 104 , 197 , 198 often utilizing EES. Localized EES using current or voltage pulses or more complex waveforms is usually delivered through microelectrodes with the aim of producing electrophysiological responses.…”

Section: Neuronal Ees In Vitromentioning

confidence: 99%

“…The in vitro control signals for closed-loop control are measures of electrical neuronal cell activity, such as local field potentials, 46 AP statistics, network burst statistics, 47 and network synchronization 48 estimates. A line of multielectrode EEM analysis methods has been presented by Ylä-Outinen et al 49 …”

Section: Introductionmentioning

confidence: 99%

Toward Closed-Loop Electrical Stimulation of Neuronal Systems: A Review

2020

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Biological neuronal cells communicate using neurochemistry and electrical signals. The same phenomena also allow us to probe and manipulate neuronal systems and communicate with them. Neuronal system malfunctions cause a multitude of symptoms and functional deficiencies that can be assessed and sometimes alleviated by electrical stimulation. Our working hypothesis is that real-time closed-loop full-duplex measurement and stimulation paradigms can provide more in-depth insight into neuronal networks and enhance our capability to control diseases of the nervous system. In this study, we review extracellular electrical stimulation methods used in in vivo , in vitro , and in silico neuroscience research and in the clinic (excluding methods mainly aimed at neuronal growth and other similar effects) and highlight the potential of closed-loop measurement and stimulation systems. A multitude of electrical stimulation and measurement-based methods are widely used in research and the clinic. Closed-loop methods have been proposed, and some are used in the clinic. However, closed-loop systems utilizing more complex measurement analysis and adaptive stimulation systems, such as artificial intelligence systems connected to biological neuronal systems, do not yet exist. Our review promotes the research and development of intelligent paradigms aimed at meaningful communications between neuronal and information and communications technology systems, “dialogical paradigms,” which have the potential to take neuroscience and clinical methods to a new level.

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Advances in Human Stem Cell-Derived Neuronal Cell Culturing and Analysis

Cited by 7 publications

References 110 publications

Astrocytes Exhibit a Protective Role in Neuronal Firing Patterns under Chemically Induced Seizures in Neuron–Astrocyte Co-Cultures

Astrocytes Exhibit a Protective Role in Neuronal Firing Patterns under Chemically Induced Seizures in Neuron–Astrocyte Co-Cultures

Human Induced Pluripotent Stem Cell‐Derived Neural Progenitor Cells Produce Distinct Neural 3D In Vitro Models Depending on Alginate/Gellan Gum/Laminin Hydrogel Blend Properties

Toward Closed-Loop Electrical Stimulation of Neuronal Systems: A Review

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