ArticleStem cells translational medicine2020
Grafted human pluripotent stem cell-derived cortical neurons integrate into adult human cortical neural circuitry.
Article in Stem cells translational medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 44 citations in OpenAlex.
- An innovative treatment for hypoxic-ischemic encephalopathy: Silk fibroin nanomaterials improve neural stem cell axon formation and facilitate cognitive improvement.Neural regeneration research · 2026Article
- Recapitulation of plaque formation, tau pathology, and neurodegeneration in a human 3D matrix model of Alzheimer's disease.Cell reports methods · 2026Article
- Electrochemical Detection of Neuronal Injury in Cell Culture Samples: A Cost-Effective Biosensor for Neurofilament Light Sensing.Biosensors · 2026Article
- Live-cell physiology in human brain tissue culture-the potential, the challenges, and the lessons learned.Frontiers in cellular neuroscience · 2026Review
- Human cortical neurons rapidly generated by embryonic stem cell programming integrate into the stroke-injured rat cortex.Stem cells (Dayton, Ohio) · 2025Article
- BDNF Overexpression Enhances Neuronal Activity and Axonal Growth in Human iPSC-Derived Neural Cultures.International journal of molecular sciences · 2025Article
- Functional recovery through the plastic adaptation of organoid grafts in cortical tissue.Cellular and molecular life sciences : CMLS · 2025Review
- Forebrain neural progenitors effectively integrate into host brain circuits and improve neural function after ischemic stroke.Nature communications · 2025Article
- Age-dependent integration of cortical progenitors transplanted at CSF-neurogenic niche interface.Frontiers in cell and developmental biology · 2025Article
- From Bench to Bedside: The Evolving Landscape of Stem Cell Therapies for Stroke Rehabilitation.Stem cells international · 2025Review
- Updated Toolbox for Assessing Neuronal Network Reconstruction after Cell Therapy.Bioengineering (Basel, Switzerland) · 2024Review
- The Role of Induced Pluripotent Stem Cells in the Treatment of Stroke.Current neuropharmacology · 2024Review
- Non-human primate models of focal cortical ischemia for neuronal replacement therapy.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Review
- Oligodendrocytes in human induced pluripotent stem cell-derived cortical grafts remyelinate adult rat and human cortical neurons.Stem cell reports · 2023Article
- Re-formation of synaptic connectivity in dissociated human stem cell-derived retinal organoid cultures.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Cortico-thalamic development and disease: From cells, to circuits, to schizophrenia.Frontiers in neuroanatomy · 2023Review
- Neuronal circuitry reconstruction after stem cell therapy in damaged brain.Neural regeneration research · 2022Article
- Physical therapy exerts sub-additive and suppressive effects on intracerebral neural stem cell implantation in a rat model of stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022Article
- Human induced pluripotent stem cells integrate, create synapses and extend long axons after spinal cord injury.Journal of cellular and molecular medicine · 2022Article
- Editor Notes: Neurogenesis and Neurodegeneration: Basic Research and Clinical applications.Stem cell reviews and reports · 2022Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Several neurodegenerative diseases cause loss of cortical neurons, leading to sensory, motor, and cognitive impairments. Studies in different animal models have raised the possibility that transplantation of human cortical neuronal progenitors, generated from pluripotent stem cells, might be developed into a novel therapeutic strategy for disorders affecting cerebral cortex. For example, we have shown that human long-term neuroepithelial-like stem (lt-NES) cell-derived cortical neurons, produced from induced pluripotent stem cells and transplanted into stroke-injured adult rat cortex, improve neurological deficits and establish both afferent and efferent morphological and functional connections with host cortical neurons. So far, all studies with human pluripotent stem cell-derived neurons have been carried out using xenotransplantation in animal models. Whether these neurons can integrate also into adult human brain circuitry is unknown. Here, we show that cortically fated lt-NES cells, which are able to form functional synaptic networks in cell culture, differentiate to mature, layer-specific cortical neurons when transplanted ex vivo onto organotypic cultures of adult human cortex. The grafted neurons are functional and establish both afferent and efferent synapses with adult human cortical neurons in the slices as evidenced by immuno-electron microscopy, rabies virus retrograde monosynaptic tracing, and whole-cell patch-clamp recordings. Our findings provide the first evidence that pluripotent stem cell-derived neurons can integrate into adult host neural networks also in a human-to-human grafting situation, thereby supporting their potential future clinical use to promote recovery by neuronal replacement in the patient's diseased brain.
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