ArticleStem cell research & therapy2019
A scalable solution for isolating human multipotent clinical-grade neural stem cells from ES precursors.
Article in Stem cell research & therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 44 citations in OpenAlex.
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- Human iPSC-derived neural stem cells displaying radial glia signature exhibit long-term safety in mice.Nature communications · 2024Article
- Stem cell-based ischemic stroke therapy: Novel modifications and clinical challenges.Asian journal of pharmaceutical sciences · 2024Review
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- Glioblastoma and cerebral organoids: development and analysis of an in vitro model for glioblastoma migration.Molecular oncology · 2023Article
- Effects of all-trans and 9-cis retinoic acid on differentiating human neural stem cells in vitro.Toxicology · 2023Article
- Single Cerebral Organoid Mass Spectrometry of Cell-Specific Protein and Glycosphingolipid Traits.Analytical chemistry · 2023Article
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- Xeno-free induced pluripotent stem cell-derived neural progenitor cells for in vivo applications.Journal of translational medicine · 2022Article
- Vesicular Glutamate Release from Feeder-FreehiPSC-Derived Neurons.International journal of molecular sciences · 2022Article
- Human iPSC-Derived Neural Models for Studying Alzheimer's Disease: from Neural Stem Cells to Cerebral Organoids.Stem cell reviews and reports · 2022Review
- The Effects of Bilirubin and Lumirubin on the Differentiation of Human Pluripotent Cell-Derived Neural Stem Cells.Antioxidants (Basel, Switzerland) · 2021Article
- LAG3 is not expressed in human and murine neurons and does not modulate α-synucleinopathies.EMBO molecular medicine · 2021Article
- Combination of Stem Cells and Rehabilitation Therapies for Ischemic Stroke.Biomolecules · 2021Review
- Targeted mass spectrometry for monitoring of neural differentiation.Biology open · 2021Article
- Global Transcriptional Analyses of the Wnt-Induced Development of Neural Stem Cells from Human Pluripotent Stem Cells.International journal of molecular sciences · 2021Article
- AAV2-mediated and hypoxia response element-directed expression of bFGF in neural stem cells showed therapeutic effects on spinal cord injury in rats.Cell death & disease · 2021Article
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Authors and funding
18 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundA well-characterized method has not yet been established to reproducibly, efficiently, and safely isolate large numbers of clinical-grade multipotent human neural stem cells (hNSCs) from embryonic stem cells (hESCs). Consequently, the transplantation of neurogenic/gliogenic precursors into the CNS for the purpose of cell replacement or neuroprotection in humans with injury or disease has not achieved widespread testing and implementation.
methodsHere, we establish an approach for the in vitro isolation of a highly expandable population of hNSCs using the manual selection of neural precursors based on their colony morphology (CoMo-NSC). The purity and NSC properties of established and extensively expanded CoMo-NSC were validated by expression of NSC markers (flow cytometry, mRNA sequencing), lack of pluripotent markers and by their tumorigenic/differentiation profile after in vivo spinal grafting in three different animal models, including (i) immunodeficient rats, (ii) immunosuppressed ALS rats (SOD1
resultsIn vitro analysis of established CoMo-NSCs showed a consistent expression of NSC markers (Sox1, Sox2, Nestin, CD24) with lack of pluripotent markers (Nanog) and stable karyotype for more than 15 passages. Gene profiling and histology revealed that spinally grafted CoMo-NSCs differentiate into neurons, astrocytes, and oligodendrocytes over a 2-6-month period in vivo without forming neoplastic derivatives or abnormal structures. Moreover, transplanted CoMo-NSCs formed neurons with synaptic contacts and glia in a variety of host environments including immunodeficient rats, immunosuppressed ALS rats (SOD1G93A), or spinally injured minipigs, indicating these cells have favorable safety and differentiation characteristics.
conclusionsThese data demonstrate that manually selected CoMo-NSCs represent a safe and expandable NSC population which can effectively be used in prospective human clinical cell replacement trials for the treatment of a variety of neurodegenerative disorders, including ALS, stroke, spinal traumatic, or spinal ischemic injury.
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