Transplanted Human Stem Cell-Derived Interneuron Precursors Mitigate Mouse Bladder Dysfunction and Central Neuropathic Pain after Spinal Cord Injury
Open accessAbstract
Neuropathic pain and bladder dysfunction represent significant quality-of-life issues for many spinal cord injury patients. Loss of GABAergic tone in the injured spinal cord may contribute to the emergence of these symptoms. Previous studies have shown that transplantation of rodent inhibitory interneuron precursors from the medial ganglionic eminence (MGE) enhances GABAergic signaling in the brain and spinal cord. Here we look at whether transplanted MGE-like cells derived from human embryonic stem cells (hESC-MGEs) can mitigate the pathological effects of spinal cord injury. We find that 6 months after transplantation into injured mouse spinal cords, hESC-MGEs differentiate into GABAergic neuron subtypes and receive synaptic inputs, suggesting functional integration into host spinal cord. Moreover, the transplanted animals show improved bladder function and mitigation of pain-related symptoms. Our results therefore suggest that this approach may be a valuable strategy for ameliorating the adverse effects of spinal cord injury.
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Human cortical interneurons have been shown to integrate extensively into the host mouse brain thanks to the remarkable migratory properties of this class of neurons.
“Human cortical interneurons have been shown to integrate extensively into the host mouse brain thanks to the remarkable migratory properties of this class of neurons”
From Xenotransplanted human cortical neurons reveal species-specific development and functional integration into mouse visual circuits (2019) · cites this paper as Fandel et al., 2016
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Hippocampal GABAergic Inhibitory Interneurons
Pelkey, K. A., Chittajallu, R., Craig, M. T., Tricoire, L., Wester, J. C., & McBain, C. J. (2017) · Physiological Reviews · doi:10.1152/physrev.00007.2017 · Cited by 889 · see citing works
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Spinal Interneurons as Gatekeepers to Neuroplasticity after Injury or Disease
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- Authors
- Fandel, T. M., Trivedi, A., Nicholas, C. R., Zhang, H., Chen, J., Martinez, A. F., Noble-Haeusslein, L. J., & Kriegstein, A. R.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Fandel, Thomas M.
- Kriegstein, Arnold R.
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2016-10
- Volume
- 19
- Issue
- 4
- Pages
- 544-557
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W2523628475
- Cited by
- 125
- References
- 4
- Citations by year
- 2026: 9 · 2025: 4 · 2024: 6 · 2023: 10 · 2022: 15 · 2021: 22 · 2020: 16 · 2019: 16 · 2018: 17 · 2017: 8 · 2016: 2
- FWCI
- 13.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- University of California, San Francisco
- National Institute of Neurological Disorders and Stroke (RC1NS068200)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Spinal Cord Injury Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- spinal cord injury, neuropathic pain, bladder dysfunction, human embryonic stem cells, medial ganglionic eminence, GABAergic interneurons, cell transplantation, GABAergic neurotransmission, functional integration, mouse model
- MeSH terms
- Human Embryonic Stem Cells, Animals, Urinary Bladder, Cell Differentiation, Cell Movement, Cell Survival, Female, Humans, Interneurons, Neuralgia, Spinal Cord Injuries, Cell Lineage, Stem Cell Transplantation, Mice
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