<i>In Vitro</i> Pain Assay Using Human iPSC-Derived Sensory Neurons and Microelectrode Array

Odawara, Aoi; Shibata, Mikako; Ishibashi, Yasuyuki; Nagafuku, Nami; Matsuda, Naoki; Suzuki, I.

doi:10.1093/toxsci/kfac045

Cited by 15 publications

(12 citation statements)

References 42 publications

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“…The number of nonspontaneous neurons was the highest at 35.65% (n = 354 neurons), and the number of neurons that were frequently spontaneously active above 10 Hz was also observed at 4.63% (n = 46 neurons). Unlike the central nervous system, DRG neurons have no synchronous activity and are spontaneous activities without synaptic transmission 41 . Figure 7B shows a 1-minute firing histogram of typical neurons firing in each frequency band.…”

Section: Spontaneous Activity Pattern Of Drg Neurons On a Cell-by-cel...mentioning

confidence: 99%

“…The toxicity evaluation of pharmaceuticals using healthy hiPSC-derived neurons 15, 17, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31 and the electrical activity analysis of neurons from diseased patients has been reported 32, 33, 34, 35, 36, 37, 38, 39, 40 . Additionally, hiPSC-derived peripheral neurons are used in evaluating pain associated with pain-related substances and anticancer drug administration compounds 41, 42, 43, 44, 45, 46 . Some brain organoids which mimic the three-dimensional structure of humans have been studied with MEA measurement method used as a functional measurement method for brain organoids 47, 48, 49, 50, 51, 52 .…”

Section: Introductionmentioning

confidence: 99%

“…This will contribute to in vitro drug efficacy assay and neurological disease research. Peripheral nerves which control pain are known to have different channels expressed in various that have different cells responses to compounds 41, 53, 54, 55, 56 . Additionally, the peripheral neuropathy by the compound is divided into toxicity to somas, axons, and myelin.…”

Section: Introductionmentioning

confidence: 99%

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Large-area electrical imaging having single neuron resolution using 236,880 electrodes CMOS-MEA technology

Suzuki

Matsuda

Han

et al. 2022

Preprint

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The electrophysiological technology having a high spatio-temporal resolution at the single-cell level, and noninvasive measurements of large areas provides insights on underlying neuronal function. Here, we used a complementary metal-oxide semiconductor (CMOS)-microelectrode array (MEA) that uses 236,880 electrodes each with an electrode size of 11.22 × 11.22 µm and 236,880 covering a wide area of 5.5 × 5.7 mm in presenting a detailed and single-cell-level neural activity analysis platform for brain slices, human iPS cell-derived cortical networks, peripheral neurons, and human brain organoids. Propagation pattern characteristics between brain regions changes the synaptic strength into compounds based on single-cell time-series patterns, classification based on single DRG neuron firing patterns and compound responses, axonal conduction characteristics and changes to anticancer drugs, and network activities and transition to compounds in brain organoids were extracted. This detailed analysis of neural activity at the single-cell level using our CMOS-MEA provides a new understanding the basic mechanisms of brain circuits in vitro and ex vivo, on human neurological diseases for drug discovery, and compound toxicity assessment.

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Section: Spontaneous Activity Pattern Of Drg Neurons On a Cell-by-cel...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Large-area electrical imaging having single neuron resolution using 236,880 electrodes CMOS-MEA technology

Suzuki

Matsuda

Han

et al. 2022

Preprint

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“…Since then, active research has been conducted mainly using rodent neurons and brain slices. With the development of human induced pluripotent stem cells (iPSCs), it is possible to induce human neurons from iPSCs, and human neural function can be evaluated in vitro ( Amin et al, 2016 ; Odawara et al, 2016 , 2022 ; Frega et al, 2017 ; Grainger et al, 2018 ; Autar et al, 2022 ; Pré et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Detection of astrocytic slow oscillatory activity and response to seizurogenic compounds using planar microelectrode array

Kuroda

Matsuda²,

Ishibashi³

et al. 2023

Front. Neurosci.

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Since the development of the planar microelectrode array (MEA), it has become popular to evaluate compounds based on the electrical activity of rodent and human induced pluripotent stem cell (iPSC)-derived neurons. However, there are no reports recording spontaneous human astrocyte activity from astrocyte-only culture sample by MEA. It is becoming clear that astrocytes play an important role in various neurological diseases, and astrocytes are expected to be excellent candidates for targeted therapeutics for the treatment of neurological diseases. Therefore, measuring astrocyte activity is very important for drug development for astrocytes. Recently, astrocyte activity has been found to be reflected in the low-frequency band < 1 Hz, which is much lower than the frequency band for recording neural activity. Here, we separated the signals obtained from human primary astrocytes cultured on MEA into seven frequency bands and successfully recorded the extracellular electrical activity of human astrocytes. The slow waveforms of spontaneous astrocyte activity were observed most clearly in direct current potentials < 1 Hz. We established nine parameters to assess astrocyte activity and evaluated five seizurogenic drug responses in human primary astrocytes and human iPSC-derived astrocytes. Astrocytes demonstrated the most significant dose-dependent changes in pilocarpine. Furthermore, in a principal component analysis using those parameter sets, the drug responses to each seizurogenic compound were separated. In this paper, we report the spontaneous electrical activity measurement of astrocytes alone using MEA for the first time and propose that the MEA measurement focusing on the low-frequency band could be useful as one of the methods to assess drug response in vitro.

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“…The following supporting information can be downloaded at: , Figure S1, Flow diagram showing the overview of the literature search; Table S1: PubMed search strategy; Table S2: Comparison of IC 50 values across different models of human induced pluripotent stem cell-derived neurons and across various chemotherapeutic agents and their applied concentrations and duration of chemotherapy exposure; Table S3: Overview of key human pharmacokinetic parameters for chemotherapeutics that cause CIPN and relevant negative controls. References [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 56 , 57 , 58 , 59 , 60 , 61 ] are cited in Supplementary Materials.…”

mentioning

confidence: 99%

Bridging the Translational Gap in Chemotherapy-Induced Peripheral Neuropathy with iPSC-Based Modeling

Mortensen

Andersen

Stage

2022

Cancers

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Chemotherapy-induced peripheral neuropathy (CIPN) is a common and potentially serious adverse effect of a wide range of chemotherapeutics. The lack of understanding of the molecular mechanisms underlying CIPN limits the efficacy of chemotherapy and development of therapeutics for treatment and prevention of CIPN. Human-induced pluripotent stem cells (iPSCs) have become an important tool to generate the cell types associated with CIPN symptoms in cancer patients. We reviewed the literature for iPSC-derived models that assessed neurotoxicity among chemotherapeutics associated with CIPN. Furthermore, we discuss the gaps in our current knowledge and provide guidance for selecting clinically relevant concentrations of chemotherapy for in vitro studies. Studies in iPSC-derived neurons revealed differential sensitivity towards mechanistically diverse chemotherapeutics associated with CIPN. Additionally, the sensitivity to chemotherapy was determined by donor background and whether the neurons had a central or peripheral nervous system identity. We propose to utilize clinically relevant concentrations that reflect the free, unbound fraction of chemotherapeutics in plasma in future studies. In conclusion, iPSC-derived sensory neurons are a valuable model to assess CIPN; however, studies in Schwann cells and motor neurons are warranted. The inclusion of multiple iPSC donors and concentrations of chemotherapy known to be achievable in patients can potentially improve translational success.

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In Vitro Pain Assay Using Human iPSC-Derived Sensory Neurons and Microelectrode Array

Cited by 15 publications

References 42 publications

Large-area electrical imaging having single neuron resolution using 236,880 electrodes CMOS-MEA technology

Large-area electrical imaging having single neuron resolution using 236,880 electrodes CMOS-MEA technology

Detection of astrocytic slow oscillatory activity and response to seizurogenic compounds using planar microelectrode array

Bridging the Translational Gap in Chemotherapy-Induced Peripheral Neuropathy with iPSC-Based Modeling

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