ArticleMolecular therapy : the journal of the American Society of Gene Therapy2015
Transplantation of glial progenitors that overexpress glutamate transporter GLT1 preserves diaphragm function following cervical SCI.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2015. 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, 41 citations in OpenAlex.
- Hepatocyte Growth Factor Delivery to Injured Cervical Spinal Cord Using an Engineered Biomaterial Protects Respiratory Neural Circuitry and Preserves Functional Diaphragm Innervation.Journal of neurotrauma · 2024Article
- PTEN inhibition promotes robust growth of bulbospinal respiratory axons and partial recovery of diaphragm function in a chronic model of cervical contusion spinal cord injury.Experimental neurology · 2024Article
- Determining Ultrasound Parameters for Bursting Polymer Microbubbles for Future Use in Spinal Cord Injury.Ultrasound in medicine & biology · 2024Article
- Glial-restricted progenitor cells: a cure for diseased brain?Biological research · 2024Review
- Article
- Review
- Astrocyte transplantation for repairing the injured spinal cord.Journal of biomedical research · 2022Article
- Review
- Reactive Astrocytes in Central Nervous System Injury: Subgroup and Potential Therapy.Frontiers in cellular neuroscience · 2021Review
- LAR inhibitory peptide promotes recovery of diaphragm function and multiple forms of respiratory neural circuit plasticity after cervical spinal cord injury.Neurobiology of disease · 2021Article
- Combination of a Gellan Gum-Based Hydrogel With Cell Therapy for the Treatment of Cervical Spinal Cord Injury.Frontiers in bioengineering and biotechnology · 2020Article
- AAV2-BDNF promotes respiratory axon plasticity and recovery of diaphragm function following spinal cord injury.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- A hydrogel engineered to deliver minocycline locally to the injured cervical spinal cord protects respiratory neural circuitry and preserves diaphragm function.Neurobiology of disease · 2019Article
- Plasticity Induced Recovery of Breathing Occurs at Chronic Stages after Cervical Contusion.Journal of neurotrauma · 2019Article
- Article
- Differential Response in Novel Stem Cell Niches of the Brain after Cervical Spinal Cord Injury and Traumatic Brain Injury.Journal of neurotrauma · 2018Article
- Mid-cervical spinal cord contusion causes robust deficits in respiratory parameters and pattern variability.Experimental neurology · 2018Article
- Local BDNF Delivery to the Injured Cervical Spinal Cord using an Engineered Hydrogel Enhances Diaphragmatic Respiratory Function.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Noninvasive imaging of nanoparticle-labeled transplant populations within polymer matrices for neural cell therapy.Nanomedicine (London, England) · 2018Article
- Improving the therapeutic efficacy of neural progenitor cell transplantation following spinal cord injury.Expert review of neurotherapeutics · 2017Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Approximately half of traumatic spinal cord injury (SCI) cases affect cervical regions, resulting in chronic respiratory compromise. The majority of these injuries affect midcervical levels, the location of phrenic motor neurons (PMNs) that innervate the diaphragm. A valuable opportunity exists following SCI for preventing PMN loss that occurs during secondary degeneration. One of the primary causes of secondary injury is excitotoxicity due to dysregulation of extracellular glutamate homeostasis. Astrocytes express glutamate transporter 1 (GLT1), which is responsible for the majority of CNS glutamate clearance. Given our observations of GLT1 dysfunction post-SCI, we evaluated intraspinal transplantation of Glial-Restricted Precursors (GRPs)--a class of lineage-restricted astrocyte progenitors--into ventral horn following cervical hemicontusion as a novel strategy for reconstituting GLT1 function, preventing excitotoxicity and protecting PMNs in the acutely injured spinal cord. We find that unmodified transplants express low levels of GLT1 in the injured spinal cord. To enhance their therapeutic properties, we engineered GRPs with AAV8 to overexpress GLT1 only in astrocytes using the GFA2 promoter, resulting in significantly increased GLT1 protein expression and functional glutamate uptake following astrocyte differentiation in vitro and after transplantation into C4 hemicontusion. Compared to medium-only control and unmodified GRPs, GLT1-overexpressing transplants reduced lesion size, diaphragm denervation and diaphragm dysfunction. Our findings demonstrate transplantation-based replacement of astrocyte GLT1 is a promising approach for SCI.
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Registered trials
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