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1

Wang, Gefei, Rui Li, Zhiwu Jiang, et al. "Influenza Virus Induces Inflammatory Response in Mouse Primary Cortical Neurons with Limited Viral Replication." BioMed Research International 2016 (2016): 1–7. http://dx.doi.org/10.1155/2016/8076989.

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Unlike stereotypical neurotropic viruses, influenza A viruses have been detected in the brain tissues of human and animal models. To investigate the interaction between neurons and influenza A viruses, mouse cortical neurons were isolated, infected with human H1N1 influenza virus, and then examined for the production of various inflammatory molecules involved in immune response. We found that replication of the influenza virus in neurons was limited, although early viral transcription was not affected. Virus-induced neuron viability decreased at 6 h postinfection (p.i.) but increased at 24 h p
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2

Häkli, Martta, Satu Jäntti, Tiina Joki, et al. "Human Neurons Form Axon-Mediated Functional Connections with Human Cardiomyocytes in Compartmentalized Microfluidic Chip." International Journal of Molecular Sciences 23, no. 6 (2022): 3148. http://dx.doi.org/10.3390/ijms23063148.

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The cardiac autonomic nervous system (cANS) regulates cardiac function by innervating cardiac tissue with axons, and cardiomyocytes (CMs) and neurons undergo comaturation during the heart innervation in embryogenesis. As cANS is essential for cardiac function, its dysfunctions might be fatal; therefore, cardiac innervation models for studying embryogenesis, cardiac diseases, and drug screening are needed. However, previously reported neuron-cardiomyocyte (CM) coculture chips lack studies of functional neuron–CM interactions with completely human-based cell models. Here, we present a novel comp
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3

Rawson, N. E., G. Gomez, B. Cowart, et al. "Selectivity and Response Characteristics of Human Olfactory Neurons." Journal of Neurophysiology 77, no. 3 (1997): 1606–13. http://dx.doi.org/10.1152/jn.1997.77.3.1606.

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Rawson, N. E., G. Gomez, B. Cowart, J. G. Brand, L. D. Lowry, E. A. Pribitkin, and D. Restrepo. Selectivity and response characteristics of human olfactory neurons. J. Neurophysiol. 77: 1606–1613, 1997. Transduction mechanisms were investigated in human olfactory neurons by determining characteristics of odorant-induced changes in intracellular calcium concentration ([Ca2+]i). Olfactory neurons were freshly isolated from nasal biopsies, allowed to attach to coverslips, and loaded with the calcium-sensitive indicator fura-2. Changes in [Ca2+]i were studied in response to exposure to individual
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4

Kraskovskaya, Nina, Anastasia Bolshakova, Mikhail Khotin, Ilya Bezprozvanny, and Natalia Mikhailova. "Protocol Optimization for Direct Reprogramming of Primary Human Fibroblast into Induced Striatal Neurons." International Journal of Molecular Sciences 24, no. 7 (2023): 6799. http://dx.doi.org/10.3390/ijms24076799.

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The modeling of neuropathology on induced neurons obtained by cell reprogramming technologies can fill a gap between clinical trials and studies on model organisms for the development of treatment strategies for neurodegenerative diseases. Patient-specific models based on patients’ cells play an important role in such studies. There are two ways to obtain induced neuronal cells. One is based on induced pluripotent stem cells. The other is based on direct reprogramming, which allows us to obtain mature neuronal cells from adult somatic cells, such as dermal fibroblasts. Moreover, the latter met
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5

Gunewardene, Niliksha, Duncan Crombie, Mirella Dottori, and Bryony A. Nayagam. "Innervation of Cochlear Hair Cells by Human Induced Pluripotent Stem Cell-Derived NeuronsIn Vitro." Stem Cells International 2016 (2016): 1–10. http://dx.doi.org/10.1155/2016/1781202.

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Induced pluripotent stem cells (iPSCs) may serve as an autologous source of replacement neurons in the injured cochlea, if they can be successfully differentiated and reconnected with residual elements in the damaged auditory system. Here, we explored the potential of hiPSC-derived neurons to innervate early postnatal hair cells, using establishedin vitroassays. We compared two hiPSC lines against a well-characterized hESC line. After ten days’ coculturein vitro, hiPSC-derived neural processes contacted inner and outer hair cells in whole cochlear explant cultures. Neural processes from hiPSC-
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6

Perego, M. Chiara, Benjamin D. McMichael, Nicholas R. McMurry, Scott W. Ventrello, and Lisa J. Bain. "Arsenic Impairs Differentiation of Human Induced Pluripotent Stem Cells into Cholinergic Motor Neurons." Toxics 11, no. 8 (2023): 644. http://dx.doi.org/10.3390/toxics11080644.

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Arsenic exposure during embryogenesis can lead to improper neurodevelopment and changes in locomotor activity. Additionally, in vitro studies have shown that arsenic inhibits the differentiation of sensory neurons and skeletal muscle. In the current study, human-induced pluripotent stem (iPS) cells were differentiated into motor neurons over 28 days, while being exposed to up to 0.5 μM arsenic. On day 6, neuroepithelial progenitor cells (NEPs) exposed to arsenic had reduced transcript levels of the neural progenitor/stem cell marker nestin (NES) and neuroepithelial progenitor marker SOX1, whil
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7

Cheng, Xueyan, Zijian Tan, Xiao Huang, et al. "Inhibition of Glioma Development by ASCL1-Mediated Direct Neuronal Reprogramming." Cells 8, no. 6 (2019): 571. http://dx.doi.org/10.3390/cells8060571.

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Direct conversion of non-neural cells into induced neurons holds great promise for brain repair. As the most common malignant tumor in the central nervous system, glioma is currently incurable due to its exponential growth and invasive behavior. Given that neurons are irreversible postmitotic cells, reprogramming glioma cells into terminally differentiated neuron-like cells represents a potential approach to inhibit brain tumor development. We here show that human glioma cells can be directly, rapidly and efficiently reprogrammed into terminally differentiated neuron-like cells by the single t
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8

Karpe, Yashashree, Zhenyu Chen, and Xue-Jun Li. "Stem Cell Models and Gene Targeting for Human Motor Neuron Diseases." Pharmaceuticals 14, no. 6 (2021): 565. http://dx.doi.org/10.3390/ph14060565.

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Motor neurons are large projection neurons classified into upper and lower motor neurons responsible for controlling the movement of muscles. Degeneration of motor neurons results in progressive muscle weakness, which underlies several debilitating neurological disorders including amyotrophic lateral sclerosis (ALS), hereditary spastic paraplegias (HSP), and spinal muscular atrophy (SMA). With the development of induced pluripotent stem cell (iPSC) technology, human iPSCs can be derived from patients and further differentiated into motor neurons. Motor neuron disease models can also be generat
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9

Tian, Jie L., Chia-Wei Huang, Farzad Eslami, Michael Philip Mannino, Rebecca Lee Mai, and Gerald W. Hart. "Regulation of Primary Cilium Length by O-GlcNAc during Neuronal Development in a Human Neuron Model." Cells 12, no. 11 (2023): 1520. http://dx.doi.org/10.3390/cells12111520.

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The primary cilium plays critical roles in the homeostasis and development of neurons. Recent studies demonstrate that cilium length is regulated by the metabolic state of cells, as dictated by processes such as glucose flux and O-GlcNAcylation (OGN). The study of cilium length regulation during neuron development, however, has been an area left largely unexplored. This project aims to elucidate the roles of O-GlcNAc in neuronal development through its regulation of the primary cilium. Here, we present findings suggesting that OGN levels negatively regulate cilium length on differentiated cort
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10

McDonald, Kirstin O., Nikita M. A. Lyons, Luca K. C. Gray, et al. "Transcription Factor-Mediated Generation of Dopaminergic Neurons from Human iPSCs—A Comparison of Methods." Cells 13, no. 12 (2024): 1016. http://dx.doi.org/10.3390/cells13121016.

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Dopaminergic neurons are the predominant brain cells affected in Parkinson’s disease. With the limited availability of live human brain dopaminergic neurons to study pathological mechanisms of Parkinson’s disease, dopaminergic neurons have been generated from human-skin-cell-derived induced pluripotent stem cells. Originally, induced pluripotent stem-cell-derived dopaminergic neurons were generated using small molecules. These neurons took more than two months to mature. However, the transcription-factor-mediated differentiation of induced pluripotent stem cells has revealed quicker and cheape
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11

Breyer, Maximilian, Stephanie Lamer, Andreas Schlosser, and Nurcan Üçeyler. "Human sensory-like neuron surfaceome analysis." PLOS ONE 20, no. 4 (2025): e0320056. https://doi.org/10.1371/journal.pone.0320056.

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Acral and triggerable pain is a hallmark of diseases involving small nerve fiber impairment, yet the underlying cellular mechanisms remain elusive. A key role is attributed to pain-related proteins located within the neuronal plasma membrane of nociceptive neurons. To explore this, we employed human induced pluripotent stem cell-derived sensory-like neurons and enriched their surface proteins by biotinylation. Samples from three independent cell differentiations were analyzed via liquid chromatography tandem mass spectrometry. Detected proteins were categorized by cellular location and functio
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12

Zhang, Shu-Zhen, Li-Xiang Ma, Wen-Jing Qian, et al. "Modeling Neurological Disease by Rapid Conversion of Human Urine Cells into Functional Neurons." Stem Cells International 2016 (2016): 1–8. http://dx.doi.org/10.1155/2016/2452985.

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Somatic cells can be directly converted into functional neurons by ectopic expression of defined factors and/or microRNAs. Since the first report of conversion mouse embryonic fibroblasts into functional neurons, the postnatal mouse, and human fibroblasts, astroglia, hepatocytes, and pericyte-derived cells have been converted into functional dopaminergic and motor neurons bothin vitroandin vivo. However, it is invasive to get all these materials. In the current study, we provide a noninvasive approach to obtain directly reprogrammed functional neurons by overexpression of the transcription fac
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13

Kanemura, Yonehiro, Hayato Fukusumi, Yukako Handa, and Tomoko Shofuda. "DDIS-30. EVALUATION OF THE SUSCEPTIBILITY OF NEURONS DERIVED FROM HUMAN INDUCED PLURIPOTENT STEM CELLS TO ANTICANCER DRUGS FOR CNS TUMORS." Neuro-Oncology 21, Supplement_6 (2019): vi69—vi70. http://dx.doi.org/10.1093/neuonc/noz175.281.

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Abstract Various chemical substances, including pharmaceuticals, pose potential risks of inducing acute or delayed neurotoxicity in adults and causing developmental neurotoxicity in fetuses or children. To ensure the safety of chemical substances and drugs, neurotoxicity risk assessment is critical, and an appropriate evaluation platform for neurotoxicity is desired. At present, several anticancer reagents, including temozolomide, cisplatin, and etoposide, are used for treatment of high-grade astrocytic tumors or medulloblastomas. In comparison to lots of information about anti-tumor cells eff
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14

Schmieder, Felix, Rouhollah Habibey, Johannes Striebel, Lars Büttner, Jürgen Czarske, and Volker Busskamp. "Tracking connectivity maps in human stem cell–derived neuronal networks by holographic optogenetics." Life Science Alliance 5, no. 7 (2022): e202101268. http://dx.doi.org/10.26508/lsa.202101268.

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Neuronal networks derived from human induced pluripotent stem cells have been exploited widely for modeling neuronal circuits, neurological diseases, and drug screening. As these networks require extended culturing periods to functionally mature in vitro, most studies are based on immature networks. To obtain insights on long-term functional features, we improved a glia–neuron co-culture protocol within multi-electrode arrays, facilitating continuous assessment of electrical features in weekly intervals. By full-field optogenetic stimulation, we detected an earlier onset of neuronal firing and
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15

Li, Minghua, Koichi Inoue, Deborah Branigan, et al. "Acid-Sensing Ion Channels in Acidosis-Induced Injury of Human Brain Neurons." Journal of Cerebral Blood Flow & Metabolism 30, no. 6 (2010): 1247–60. http://dx.doi.org/10.1038/jcbfm.2010.30.

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Acidosis is a common feature of the human brain during ischemic stroke and is known to cause neuronal injury. However, the mechanism underlying acidosis-mediated injury of the human brain remains elusive. We show that a decrease in the extracellular pH evoked inward currents characteristic of acid-sensing ion channels (ASICs) and increased intracellular Ca2+ in cultured human cortical neurons. Acid-sensing ion channels in human cortical neurons show electrophysiological and pharmacological properties distinct from those in neurons of the rodent brain. Reverse transcriptase-PCR and western blot
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16

Neunlist, M., J. Barouk, K. Michel та ін. "Toxin B ofClostridium difficileactivates human VIP submucosal neurons, in part via an IL-1β-dependent pathway". American Journal of Physiology-Gastrointestinal and Liver Physiology 285, № 5 (2003): G1049—G1055. http://dx.doi.org/10.1152/ajpgi.00487.2002.

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This study investigated whether toxin B of Clostridium difficile can activate human submucosal neurons and the involved pathways. Isolated segments of human colon were placed in organ culture for 3 h in the presence of toxin B or IL-1β. Whole mounts of internal submucosal plexus were stained with antibodies against c-Fos, neuron-specific enolase (NSE), vasoactive intestinal polypeptide (VIP), and substance P (SP). The membrane potential (Vm) response of submucosal neurons to local application of toxin B and IL-1β was determined by a multisite optical recording technique. Toxin B (0.1 to 10 ng/
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17

Shin, Grace Ji-eun, Maria Elena Pero, Luke A. Hammond, et al. "Integrins protect sensory neurons in models of paclitaxel-induced peripheral sensory neuropathy." Proceedings of the National Academy of Sciences 118, no. 15 (2021): e2006050118. http://dx.doi.org/10.1073/pnas.2006050118.

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Chemotherapy-induced peripheral neuropathy (CIPN) is a major side effect from cancer treatment with no known method for prevention or cure in clinics. CIPN often affects unmyelinated nociceptive sensory terminals. Despite the high prevalence, molecular and cellular mechanisms that lead to CIPN are still poorly understood. Here, we used a genetically tractableDrosophilamodel and primary sensory neurons isolated from adult mouse to examine the mechanisms underlying CIPN and identify protective pathways. We found that chronic treatment ofDrosophilalarvae with paclitaxel caused degeneration and al
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18

Kondo, Tosho, Ihori Ebinuma, Hirotaka Tanaka, et al. "Rapid and Robust Multi-Phenotypic Assay System for ALS Using Human iPS Cells with Mutations in Causative Genes." International Journal of Molecular Sciences 24, no. 8 (2023): 6987. http://dx.doi.org/10.3390/ijms24086987.

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Amyotrophic lateral sclerosis (ALS) is a major life-threatening disease caused by motor neuron degeneration. More effective treatments through drug discovery are urgently needed. Here, we established an effective high-throughput screening system using induced pluripotent stem cells (iPSCs). Using a Tet-On-dependent transcription factor expression system carried on the PiggyBac vector, motor neurons were efficiently and rapidly generated from iPSCs by a single-step induction method. Induced iPSC transcripts displayed characteristics similar to those of spinal cord neurons. iPSC-generated motor
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19

Patel, Charvi A., Muhammad Mukhtar, and Roger J. Pomerantz. "Human Immunodeficiency Virus Type 1 Vpr Induces Apoptosis in Human Neuronal Cells." Journal of Virology 74, no. 20 (2000): 9717–26. http://dx.doi.org/10.1128/jvi.74.20.9717-9726.2000.

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ABSTRACT Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system (CNS) causes AIDS dementia complex (ADC) in certain infected individuals. Recent studies have suggested that patients with ADC have an increased incidence of neuronal apoptosis leading to neuronal dropout. Of note, a higher level of the HIV-1 accessory protein Vpr has been detected in the cerebrospinal fluid of AIDS patients with neurological disorders. Moreover, extracellular Vpr has been shown to form ion channels, leading to cell death of cultured rat hippocampal neurons. Based on these previous fin
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20

Ryding, Matias, Mattias Gamre, Mette S. Nissen, et al. "Neurodegeneration Induced by Anti-IgLON5 Antibodies Studied in Induced Pluripotent Stem Cell-Derived Human Neurons." Cells 10, no. 4 (2021): 837. http://dx.doi.org/10.3390/cells10040837.

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Anti-IgLON5 disease is a progressive neurological disorder associated with autoantibodies against a neuronal cell adhesion molecule, IgLON5. In human postmortem brain tissue, the neurodegeneration and accumulation of hyperphosphorylated tau (p-tau) are found. Whether IgLON5 antibodies induce neurodegeneration or neurodegeneration provokes an immune response causing inflammation and antibody formation remains to be elucidated. We investigated the effects of anti-IgLON5 antibodies on human neurons. Human neural stem cells were differentiated for 14–48 days and exposed from Days 9 to 14 (short-te
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Juntunen, Miia, Sanna Hagman, Anaick Moisan, Susanna Narkilahti, and Susanna Miettinen. "In Vitro Oxygen-Glucose Deprivation-Induced Stroke Models with Human Neuroblastoma Cell- and Induced Pluripotent Stem Cell-Derived Neurons." Stem Cells International 2020 (October 29, 2020): 1–13. http://dx.doi.org/10.1155/2020/8841026.

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Stroke is a devastating neurological disorder and one of the leading causes of mortality and disability. To understand the cellular and molecular mechanisms of stroke and to develop novel therapeutic approaches, two different in vitro human cell-based stroke models were established using oxygen-glucose deprivation (OGD) conditions. In addition, the effect of adipose stem cells (ASCs) on OGD-induced injury was studied. In the present study, SH-SY5Y human neuroblastoma cells and human induced pluripotent stem cells (hiPSCs) were differentiated into neurons, cultured under OGD conditions (1% O2)
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22

Voronkov, Dmitry N., Alla V. Stavrovskaya, Olga S. Lebedeva, et al. "Morphological Changes in Neural Progenitors Derived from Human Induced Pluripotent Stem Cells and Transplanted into the Striatum of a Parkinson's Disease Rat Model." Annals of Clinical and Experimental Neurology 17, no. 2 (2023): 43–50. http://dx.doi.org/10.54101/acen.2023.2.6.

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Introduction. Development of cell therapy for Parkinson's disease (PD) requires protocols based on transplantation of neurons derived from human induced pluripotent stem cells (hiPSCs) into the damaged area of the brain.
 Objective: to characterize neurons transplanted into a rat brain and evaluate neural transplantation efficacy using a PD animal model.
 Materials and methods. Neurons derived from hiPSCs (IPSRG4S line) were transplanted into the striatum of rats after intranigral injection of 6-hydroxydopamine (6-OHDA). Immunostaining was performed to identify expression of glial an
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23

Winbo, Annika, Suganeya Ramanan, Emily Eugster, Stefan Jovinge, Jonathan R. Skinner, and Johanna M. Montgomery. "Functional coculture of sympathetic neurons and cardiomyocytes derived from human-induced pluripotent stem cells." American Journal of Physiology-Heart and Circulatory Physiology 319, no. 5 (2020): H927—H937. http://dx.doi.org/10.1152/ajpheart.00546.2020.

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We present data on a functional coculture between human-induced pluripotent stem cell-derived sympathetic neurons and cardiomyocytes. Moreover, this study adds significantly to the available data on the electrophysiological function of human-induced pluripotent stem cell-derived sympathetic neurons.
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24

Hood, Chantelle, Anthony L. Cunningham, Barry Slobedman, et al. "Varicella-Zoster Virus ORF63 Inhibits Apoptosis of Primary Human Neurons." Journal of Virology 80, no. 2 (2006): 1025–31. http://dx.doi.org/10.1128/jvi.80.2.1025-1031.2006.

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ABSTRACT Virus-encoded modulation of apoptosis may serve as a mechanism to enhance cell survival and virus persistence. The impact of productive varicella-zoster virus (VZV) infection on apoptosis appears to be cell type specific, as infected human sensory neurons are resistant to apoptosis, yet human fibroblasts readily become apoptotic. We sought to identify the viral gene product(s) responsible for this antiapoptotic phenotype in primary human sensory neurons. Treatment with phosphonoacetic acid to inhibit viral DNA replication and late-phase gene expression did not alter the antiapoptotic
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25

Yu, Yong-Qiang, Lian-Cheng Liu, Fa-Cai Wang, et al. "Induction Profile of MANF/ARMET by Cerebral Ischemia and its Implication for Neuron Protection." Journal of Cerebral Blood Flow & Metabolism 30, no. 1 (2009): 79–91. http://dx.doi.org/10.1038/jcbfm.2009.181.

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Cerebral ischemia-induced accumulation of unfolded proteins in vulnerable neurons triggers endoplasmic reticulum (ER) stress. Arginine-rich, mutated in early stage tumors (ARMET) is an ER stress-inducible protein and upregulated in the early stage of cerebral ischemia. The purposes of this study were to investigate the characteristics and implications of ARMET expression induced by focal cerebral ischemia. Focal cerebral ischemia in rats was induced by right middle cerebral artery occlusion with a suture; ischemic lesions were assessed by magnetic resonance imaging and histology; neuronal apop
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26

Brot, Sébastien, Nabila Pyrenina Thamrin, Marie-Laure Bonnet, et al. "Long-Term Evaluation of Intranigral Transplantation of Human iPSC-Derived Dopamine Neurons in a Parkinson’s Disease Mouse Model." Cells 11, no. 10 (2022): 1596. http://dx.doi.org/10.3390/cells11101596.

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Parkinson’s disease (PD) is a neurodegenerative disorder associated with loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). One strategy for treating PD is transplantation of DA neuroblasts. Significant advances have been made in generating midbrain DA neurons from human pluripotent stem cells. Before these cells can be routinely used in clinical trials, extensive preclinical safety studies are required. One of the main issues to be addressed is the long-term therapeutic effectiveness of these cells. In most transplantation studies using human cells, the maturation
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27

Cresto, Noémie, Camille Gardier, Marie-Claude Gaillard та ін. "The C-Terminal Domain of LRRK2 with the G2019S Substitution Increases Mutant A53T α-Synuclein Toxicity in Dopaminergic Neurons In Vivo". International Journal of Molecular Sciences 22, № 13 (2021): 6760. http://dx.doi.org/10.3390/ijms22136760.

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Alpha-synuclein (α-syn) and leucine-rich repeat kinase 2 (LRRK2) play crucial roles in Parkinson’s disease (PD). They may functionally interact to induce the degeneration of dopaminergic (DA) neurons via mechanisms that are not yet fully understood. We previously showed that the C-terminal portion of LRRK2 (ΔLRRK2) with the G2019S mutation (ΔLRRK2G2019S) was sufficient to induce neurodegeneration of DA neurons in vivo, suggesting that mutated LRRK2 induces neurotoxicity through mechanisms that are (i) independent of the N-terminal domains and (ii) “cell-autonomous”. Here, we explored whether Δ
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28

Kong, K., C. Ukachoke, P. Ashby, and K. R. Chapman. "Excitability of human motor cortex during hyperventilation and hypercapnia." Canadian Journal of Physiology and Pharmacology 72, no. 8 (1994): 909–13. http://dx.doi.org/10.1139/y94-128.

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We tested the hypothesis that the excitability of corticospinal neurons was altered by changes in [Formula: see text]. Magnetic stimulation was used to excite the neurons in the human motor cortex that give rise to the fast-conducting corticospinal pathway. The characteristics of the composite excitatory postsynaptic potentials (EPSPs) produced in individual spinal motoneurons by cortical stimulation were derived from changes in the firing probability of voluntarily activated motor units. The amplitudes of these composite EPSPs in response to a constant cortical stimulus were assumed to reflec
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Imran, Saima Jalil, Barbora Vagaska, Jan Kriska, et al. "Aryl Hydrocarbon Receptor (AhR)-Mediated Signaling in iPSC-Derived Human Motor Neurons." Pharmaceuticals 15, no. 7 (2022): 828. http://dx.doi.org/10.3390/ph15070828.

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Exposure to environmental pollutants and endogenous metabolites that induce aryl hydrocarbon receptor (AhR) expression has been suggested to affect cognitive development and, particularly in boys, also motor function. As current knowledge is based on epidemiological and animal studies, in vitro models are needed to better understand the effects of these compounds in the human nervous system at the molecular level. Here, we investigated expression of AhR pathway components and how they are regulated by AhR ligands in human motor neurons. Motor neurons generated from human induced pluripotent st
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Mariani, Alessandro, Davide Comolli, Roberto Fanelli, Gianluigi Forloni, and Massimiliano De Paola. "Neonicotinoid Pesticides Affect Developing Neurons in Experimental Mouse Models and in Human Induced Pluripotent Stem Cell (iPSC)-Derived Neural Cultures and Organoids." Cells 13, no. 15 (2024): 1295. http://dx.doi.org/10.3390/cells13151295.

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Neonicotinoids are synthetic, nicotine-derived insecticides used worldwide to protect crops and domestic animals from pest insects. The reported evidence shows that they are also able to interact with mammalian nicotine receptors (nAChRs), triggering detrimental responses in cultured neurons. Exposure to high neonicotinoid levels during the fetal period induces neurotoxicity in animal models. Considering the persistent exposure to these insecticides and the key role of nAChRs in brain development, their potential neurotoxicity on mammal central nervous system (CNS) needs further investigations
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Bachmann, Sarah, Jenice Linde, Michael Bell, Marc Spehr, Hans Zempel, and Geraldine Zimmer-Bensch. "DNA Methyltransferase 1 (DNMT1) Shapes Neuronal Activity of Human iPSC-Derived Glutamatergic Cortical Neurons." International Journal of Molecular Sciences 22, no. 4 (2021): 2034. http://dx.doi.org/10.3390/ijms22042034.

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Epigenetic mechanisms are emerging key players for the regulation of brain function, synaptic activity, and the formation of neuronal engrams in health and disease. As one important epigenetic mechanism of transcriptional control, DNA methylation was reported to distinctively modulate synaptic activity in excitatory and inhibitory cortical neurons in mice. Since DNA methylation signatures are responsive to neuronal activity, DNA methylation seems to contribute to the neuron’s capacity to adapt to and integrate changing activity patterns, being crucial for the plasticity and functionality of ne
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Bufalo, Michelle Cristiane, Maíra Estanislau Soares de Almeida, José Ricardo Jensen, et al. "Human Sensory Neuron-like Cells and Glycated Collagen Matrix as a Model for the Screening of Analgesic Compounds." Cells 11, no. 2 (2022): 247. http://dx.doi.org/10.3390/cells11020247.

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Increased collagen-derived advanced glycation end-products (AGEs) are consistently related to painful diseases, including osteoarthritis, diabetic neuropathy, and neurodegenerative disorders. We have recently developed a model combining a two-dimensional glycated extracellular matrix (ECM-GC) and primary dorsal root ganglion (DRG) that mimicked a pro-nociceptive microenvironment. However, culturing primary cells is still a challenge for large-scale screening studies. Here, we characterized a new model using ECM-GC as a stimulus for human sensory-like neurons differentiated from SH-SY5Y cell li
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Halliwell, Robert F., Hamed Salmanzadeh, Leanne Coyne, and William S. Cao. "An Electrophysiological and Pharmacological Study of the Properties of Human iPSC-Derived Neurons for Drug Discovery." Cells 10, no. 8 (2021): 1953. http://dx.doi.org/10.3390/cells10081953.

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Human stem cell-derived neurons are increasingly considered powerful models in drug discovery and disease modeling, despite limited characterization of their molecular properties. Here, we have conducted a detailed study of the properties of a commercial human induced Pluripotent Stem Cell (iPSC)-derived neuron line, iCell [GABA] neurons, maintained for up to 3 months in vitro. We confirmed that iCell neurons display neurite outgrowth within 24 h of plating and label for the pan-neuronal marker, βIII tubulin within the first week. Our multi-electrode array (MEA) recordings clearly showed neuro
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34

Jongkamonwiwat, Nopporn, and Parinya Noisa. "Biomedical and Clinical Promises of Human Pluripotent Stem Cells for Neurological Disorders." BioMed Research International 2013 (2013): 1–10. http://dx.doi.org/10.1155/2013/656531.

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Neurological disorders are characterized by the chronic and progressive loss of neuronal structures and functions. There is a variability of the onsets and causes of clinical manifestations. Cell therapy has brought a new concept to overcome brain diseases, but the advancement of this therapy is limited by the demands of specialized neurons. Human pluripotent stem cells (hPSCs) have been promised as a renewable resource for generating human neurons for both laboratory and clinical purposes. By the modulations of appropriate signalling pathways, desired neuron subtypes can be obtained, and indu
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Wu, Xunyi, Zhiyun Chen, Wanbing Sun, et al. "Activation of Kir2.3 Channels by Tenidap Suppresses Epileptiform Burst Discharges in Cultured Hippocampal Neurons." CNS & Neurological Disorders - Drug Targets 18, no. 8 (2019): 621–30. http://dx.doi.org/10.2174/1871527318666190807122623.

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Background & Objective: Tenidap, a selective human inwardly rectifying potassium (Kir) 2.3 channel opener, has been reported to have antiepileptic effect in the pilocarpine temporal lobe epilepsy rat model in our previous study. However, the effect of tenidap on neurons and its relationship with the epileptiform bursting charges in neuron is still required to be explored. Methods: In this study, cyclothiazide (CTZ) induced cultured hippocampal neuron epileptic model was used to study the antiepileptic effect of tenidap and the relationship between Kir2.3 channel and the neuronal epileptifo
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Jansch, Charline, Georg C. Ziegler, Andrea Forero, et al. "Serotonin-specific neurons differentiated from human iPSCs form distinct subtypes with synaptic protein assembly." Journal of Neural Transmission 128, no. 2 (2021): 225–41. http://dx.doi.org/10.1007/s00702-021-02303-5.

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AbstractHuman induced pluripotent stem cells (hiPSCs) have revolutionized the generation of experimental disease models, but the development of protocols for the differentiation of functionally active neuronal subtypes with defined specification is still in its infancy. While dysfunction of the brain serotonin (5-HT) system has been implicated in the etiology of various neuropsychiatric disorders, investigation of functional human 5-HT specific neurons in vitro has been restricted by technical limitations. We describe an efficient generation of functionally active neurons from hiPSCs displayin
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Carsana, Emma Veronica, Matteo Audano, Silvia Breviario, et al. "Metabolic Profile Variations along the Differentiation of Human-Induced Pluripotent Stem Cells to Dopaminergic Neurons." Biomedicines 10, no. 9 (2022): 2069. http://dx.doi.org/10.3390/biomedicines10092069.

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In recent years, the availability of induced pluripotent stem cell-based neuronal models has opened new perspectives on the study and therapy of neurological diseases such as Parkinson’s disease. In particular, P. Zhang set up a protocol to efficiently generate dopaminergic neurons from induced pluripotent stem cells. Although the differentiation process of these cells has been widely investigated, there is scant information related to the variation in metabolic features during the differentiation process of pluripotent stem cells to mature dopaminergic neurons. For this reason, we analysed th
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Akter, Masuma, and Baojin Ding. "Modeling Movement Disorders via Generation of hiPSC-Derived Motor Neurons." Cells 11, no. 23 (2022): 3796. http://dx.doi.org/10.3390/cells11233796.

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Generation of motor neurons (MNs) from human-induced pluripotent stem cells (hiPSCs) overcomes the limited access to human brain tissues and provides an unprecedent approach for modeling MN-related diseases. In this review, we discuss the recent progression in understanding the regulatory mechanisms of MN differentiation and their applications in the generation of MNs from hiPSCs, with a particular focus on two approaches: induction by small molecules and induction by lentiviral delivery of transcription factors. At each induction stage, different culture media and supplements, typical growth
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Real, Raquel, Manuel Peter, Antonio Trabalza, et al. "In vivo modeling of human neuron dynamics and Down syndrome." Science 362, no. 6416 (2018): eaau1810. http://dx.doi.org/10.1126/science.aau1810.

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Harnessing the potential of human stem cells for modeling the physiology and diseases of cortical circuitry requires monitoring cellular dynamics in vivo. We show that human induced pluripotent stem cell (iPSC)–derived cortical neurons transplanted into the adult mouse cortex consistently organized into large (up to ~100 mm3) vascularized neuron-glia territories with complex cytoarchitecture. Longitudinal imaging of >4000 grafted developing human neurons revealed that neuronal arbors refined via branch-specific retraction; human synaptic networks substantially restructured over 4 months, wi
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Chen, Yalan, Junxin Kuang, Yimei Niu, et al. "Multiple factors to assist human-derived induced pluripotent stem cells to efficiently differentiate into midbrain dopaminergic neurons." Neural Regeneration Research 19, no. 4 (2023): 908–14. http://dx.doi.org/10.4103/1673-5374.378203.

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JOURNAL/nrgr/04.03/01300535-202404000-00037/inline-graphic1/v/2023-09-09T133047Z/r/image-tiff Midbrain dopaminergic neurons play an important role in the etiology of neurodevelopmental and neurodegenerative diseases. They also represent a potential source of transplanted cells for therapeutic applications. In vitro differentiation of functional midbrain dopaminergic neurons provides an accessible platform to study midbrain neuronal dysfunction and can be used to examine obstacles to dopaminergic neuronal development. Emerging evidence and impressive advances in human induced pluripotent stem c
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Huang, Jingyuan, Yan Xu, Fang Wang, et al. "Long Noncoding RNA SPRY4-IT1 Modulates Ketamine-Induced Neurotoxicity in Human Embryonic Stem Cell-Derived Neurons through EZH2." Developmental Neuroscience 43, no. 1 (2021): 9–17. http://dx.doi.org/10.1159/000513535.

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<b><i>Objective:</i></b> This study aimed to investigate whether long noncoding RNA sprouty receptor tyrosine kinase signaling antagonist 4-intronic transcript 1 (SPRY4-IT1) is involved in the regulation of ketamine-induced neurotoxicity. <b><i>Methods:</i></b> Human embryonic stem cells (hESCs) were induced into neurons in vitro and treated with ketamine. Apoptosis and neurite degeneration assays were used to determine ketamine-induced neurotoxicity and qRT-PCR to determine SPRY4-IT1 expression. SPRY4-IT1 was downregulated in hESC-induced neuron
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Xu, Z., H. Jiang, P. Zhong, Z. Yan, S. Chen, and J. Feng. "Direct conversion of human fibroblasts to induced serotonergic neurons." Molecular Psychiatry 21, no. 1 (2015): 62–70. http://dx.doi.org/10.1038/mp.2015.101.

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43

Adelman, Jacob W., Suzette Rosas-Rogers, Megan L. Schumacher, Rebekah L. Mokry, Scott S. Terhune, and Allison D. Ebert. "Human cytomegalovirus induces significant structural and functional changes in terminally differentiated human cortical neurons." mBio, November 15, 2023. http://dx.doi.org/10.1128/mbio.02251-23.

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ABSTRACT Human cytomegalovirus (HCMV) is a highly prevalent viral pathogen that typically presents asymptomatically in healthy individuals despite lifelong latency. However, in 10%–15% of congenital cases, this beta-herpesvirus demonstrates direct effects on the central nervous system, including microcephaly, cognitive and learning delays, and hearing deficits. HCMV has been widely shown to infect neural progenitor cells, but the permissiveness of fully differentiated neurons to HCMV is controversial and chronically understudied, despite potential associations between HCMV infection and neurod
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Zhang, Jun, Zhifu Chen, Xiaoyan Luo, and Zhoujing Yang. "TrkC Overexpression Protects Sevoflurane-Induced Neurotoxicity in Human Induced Pluripotent Stem Cell-Derived Neurons." Developmental Neuroscience, October 26, 2020, 1–9. http://dx.doi.org/10.1159/000510326.

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<b><i>Background:</i></b> Inhaled anesthetic sevoflurane (SEVO) may induce cortical neurotoxicity and memory dysfunction in both animals and humans. In this study, we investigated the toxic effects of SEVO on human induced pluripotent stem cell (iPS)-derived neurons. <b><i>Methods:</i></b> Human iPS-derived neurons were exposed to SEVO in vitro. SEVO-induced toxic effects were examined with the viability, live caspase 3/7, and neurite density assays, respectively. The effects of SEVO on the receptors of the tyrosine kinases TrkA, TrkB, and TrkC w
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Liu, Yingfei, Jinzhao Wang, Thomas C. Südhof, and Marius Wernig. "Efficient generation of functional neurons from mouse embryonic stem cells via Neurogenin-2 expression." February 9, 2023. https://doi.org/10.5281/zenodo.7625605.

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The production of induced neuronal (iN) cells from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) by the forced expression of proneural transcription factors is rapid, efficient, and reproducible. The ability to generate large numbers of human neurons in such a robust manner enables large-scale studies of human neural differentiation and neuropsychiatric diseases. Surprisingly, similar transcription factor-based approaches for converting mouse ESCs into iN cells have been challenging, primarily due to low cell survival. Here, we provide a detailed approach for the
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Halonen, Sandra K. "Use of in vitro derived human neuronal models to study host-parasite interactions of Toxoplasma gondii in neurons and neuropathogenesis of chronic toxoplasmosis." Frontiers in Cellular and Infection Microbiology 13 (March 8, 2023). http://dx.doi.org/10.3389/fcimb.2023.1129451.

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Toxoplasma gondii infects approximately one-third of the world’s population resulting in a chronic infection with the parasite located in cysts in neurons in the brain. In most immunocompetent hosts the chronic infection is asymptomatic, but several studies have found correlations between Toxoplasma seropositivity and neuropsychiatric disorders, including Schizophrenia, and some other neurological disorders. Host-parasite interactions of bradyzoites in cysts in neurons is not well understood due in part to the lack of suitable in vitro human neuronal models. The advent of stem cell technologie
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Qin, Hua, An-Dong Zhao, Meng-Li Sun, Kui Ma, and Xiao-Bing Fu. "Direct conversion of human fibroblasts into dopaminergic neuron-like cells using small molecules and protein factors." Military Medical Research 7, no. 1 (2020). http://dx.doi.org/10.1186/s40779-020-00284-2.

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Abstract Background Generation of neurons is essential in cell replacement therapy for neurodegenerative disorders like Parkinson’s disease. Several studies have reported the generation of dopaminergic (DA) neurons from mouse and human fibroblasts by ectopic expression of transcription factors, in which genetic manipulation is associated with potential risks. Methods The small molecules and protein factors were selected based on their function to directly induce human fetal lung IMR-90 fibroblasts into DA neuron-like cells. Microscopical, immunocytochemical, and RT-qPCR analyses were used to c
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Sepehrimanesh, Masood, Wu Xu, and Baojin Ding. "Comparative analysis of chemical and lentiviral approaches in the generation of human induced pluripotent stem cell–derived motor neurons." Neural Regeneration Research, May 6, 2025. https://doi.org/10.4103/nrr.nrr-d-24-00435.

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Abstract The generation of human induced pluripotent stem cell-derived motor neurons overcomes limited access to human tissues and offers an unprecedented approach to modeling motor neuron diseases such as dystonia and amyotrophic lateral sclerosis. Motor neurons generated through different strategies may exhibit substantial differences in purity, maturation, characterization, and even neuronal identity, leading to variable outcomes in disease modeling and drug screening. However, very few comparative studies have been conducted to determine the similarities and differences among motor neurons
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Hulme, Amy J., Jeffrey R. McArthur, Simon Maksour, et al. "Molecular and Functional Characterization of Neurogenin-2 Induced Human Sensory Neurons." Frontiers in Cellular Neuroscience 14 (December 4, 2020). http://dx.doi.org/10.3389/fncel.2020.600895.

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Sensory perception is fundamental to everyday life, yet understanding of human sensory physiology at the molecular level is hindered due to constraints on tissue availability. Emerging strategies to study and characterize peripheral neuropathies in vitro involve the use of human pluripotent stem cells (hPSCs) differentiated into dorsal root ganglion (DRG) sensory neurons. However, neuronal functionality and maturity are limited and underexplored. A recent and promising approach for directing hPSC differentiation towards functionally mature neurons involves the exogenous expression of Neurogeni
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Smulders, Pascal S. H., Kim Heikamp, Jeroen Hermanides, Markus W. Hollmann, Werner ten Hoope, and Nina C. Weber. "Chemotherapy-induced peripheral neuropathy models constructed from human induced pluripotent stem cells and directly converted cells: a systematic review." Pain, February 21, 2024. http://dx.doi.org/10.1097/j.pain.0000000000003193.

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Abstract Developments in human cellular reprogramming now allow for the generation of human neurons for in vitro disease modelling. This technique has since been used for chemotherapy-induced peripheral neuropathy (CIPN) research, resulting in the description of numerous CIPN models constructed from human neurons. This systematic review provides a critical analysis of available models and their methodological considerations (ie, used cell type and source, CIPN induction strategy, and validation method) for prospective researchers aiming to incorporate human in vitro models of CIPN in their res
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