ArticleStem cells translational medicine2015
NG2+ progenitors derived from embryonic stem cells penetrate glial scar and promote axonal outgrowth into white matter after spinal cord injury.
Article in Stem cells translational medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 41 citations in OpenAlex.
- Research progress of hydrogels as delivery systems and scaffolds in the treatment of secondary spinal cord injury.Frontiers in bioengineering and biotechnology · 2023Review
- Water Treadmill Training Ameliorates Neurite Outgrowth Inhibition Associated with NGR/RhoA/ROCK by Inhibiting Astrocyte Activation following Spinal Cord Injury.Oxidative medicine and cellular longevity · 2022Article
- Review
- Novel instrumented frame for standing exercising of users with complete spinal cord injuries.Scientific reports · 2019Article
- NrCAM is a marker for substrate-selective activation of ADAM10 in Alzheimer's disease.EMBO molecular medicine · 2019Article
- Injectable polypeptide hydrogels via methionine modification for neural stem cell delivery.Biomaterials · 2018Article
- Local inhibition of matrix metalloproteinases reduced M2 macrophage activity and impeded recovery in spinal cord transected rats after treatment with fibroblast growth factor-1 and nerve grafts.Neural regeneration research · 2018Article
- Review
- Retinoic acid synthesis by NG2 expressing cells promotes a permissive environment for axonal outgrowth.Neurobiology of disease · 2018Article
- Three-dimensional Tissue Engineered Aligned Astrocyte Networks to Recapitulate Developmental Mechanisms and Facilitate Nervous System Regeneration.Journal of visualized experiments : JoVE · 2018Article
- Gene silencing NMII promotes axonal regeneration against contusive spinal cord injury in rats.International journal of clinical and experimental pathology · 2017Article
- Does the preclinical evidence for functional remyelination following myelinating cell engraftment into the injured spinal cord support progression to clinical trials?Experimental neurology · 2016Review
- Extrinsic and Intrinsic Regulation of Axon Regeneration by MicroRNAs after Spinal Cord Injury.Neural plasticity · 2016Review
- Stem Cell Therapy for Spinal Cord Injury.Cell transplantationArticle
- Cell Transplantation for Repair of the Spinal Cord and Prospects for Generating Region-Specific Exogenic Neuronal Cells.Cell transplantationReview
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
The glial scar resulting from spinal cord injury is rich in chondroitin sulfate proteoglycan (CSPG), a formidable barrier to axonal regeneration. We explored the possibility of breaching that barrier by first examining the scar in a functional in vitro model. We found that embryonic stem cell-derived neural lineage cells (ESNLCs) with prominent expression of nerve glial antigen 2 (NG2) survived, passed through an increasingly inhibitory gradient of CSPG, and expressed matrix metalloproteinase 9 (MMP-9) at the appropriate stage of their development. Outgrowth of axons from ESNLCs followed because the migrating cells sculpted pathways in which CSPG was degraded. The degradative mechanism involved MMP-9 but not MMP-2. To confirm these results in vivo, we transplanted ESNLCs directly into the cavity of a contused spinal cord 9 days after injury. A week later, ESNLCs survived and were expressing both NG2 and MMP-9. Their axons had grown through long distances (>10 mm), although they preferred to traverse white rather than gray matter. These data are consistent with the concept that expression of inhibitory CSPG within the injury scar is an important impediment to regeneration but that NG2+ progenitors derived from ESNLCs can modify the microenvironment to allow axons to grow through the barrier. This beneficial action may be partly due to developmental expression of MMP-9. We conclude that it might eventually be possible to encourage axonal regeneration in the human spinal cord by transplanting ESNLCs or other cells that express NG2.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.