ArticleTissue engineering. Part A2015
Finely Tuned Temporal and Spatial Delivery of GDNF Promotes Enhanced Nerve Regeneration in a Long Nerve Defect Model.
Article in Tissue engineering. Part A, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- Animal models in peripheral nerve transection studies: a systematic review on study design and outcomes assessment.Regenerative medicine · 2024Pooled it
- Regenerative Endodontic Therapies: Harnessing Stem Cells, Scaffolds, and Growth Factors.Polymers · 2025Review
- Optimizing Peripheral Nerve Regeneration: Surgical Techniques, Biomolecular and Regenerative Strategies-A Narrative Review.International journal of molecular sciences · 2025Review
- The Physiologic Basis of Molecular Therapeutics for Peripheral Nerve Injury: A Primer.Journal of hand surgery global online · 2024Review
- Limited Nerve Regeneration across Acellular Nerve Allografts (ANAs) Coincides with Changes in Blood Vessel Morphology and the Development of a Pro-Inflammatory Microenvironment.International journal of molecular sciences · 2024Article
- Gene Therapy for Regenerative Medicine.Pharmaceutics · 2023Review
- Delay modulates the immune response to nerve repair.NPJ Regenerative medicine · 2023Article
- Engineered Schwann Cell-Based Therapies for Injury Peripheral Nerve Reconstruction.Frontiers in cellular neuroscience · 2022Review
- Syndecan-3 contributes to the regulation of the microenvironment at the node of Ranvier following end-to‑side neurorrhaphy: sodium image analysis.Histochemistry and cell biology · 2021Article
- Liposomes embedded within fibrin gels facilitate localized macrophage manipulations within nerve.Journal of neuroscience methods · 2021Article
- Mouse Embryonic Stem Cells Expressing GDNF Show Enhanced Dopaminergic Differentiation and Promote Behavioral Recovery After Grafting in Parkinsonian Rats.Frontiers in cell and developmental biology · 2021Article
- Decellularization of Nervous Tissues and Clinical Application.Advances in experimental medicine and biology · 2021Article
- Designer, injectable gels to prevent transplanted Schwann cell loss during spinal cord injury therapy.Science advances · 2020Article
- GDNF Gene Therapy to Repair the Injured Peripheral Nerve.Frontiers in bioengineering and biotechnology · 2020Review
- Imaging in the repair of peripheral nerve injury.Nanomedicine (London, England) · 2019Article
- Modern Trends for Peripheral Nerve Repair and Regeneration: Beyond the Hollow Nerve Guidance Conduit.Frontiers in bioengineering and biotechnology · 2019Review
- A Subtle Network Mediating Axon Guidance: Intrinsic Dynamic Structure of Growth Cone, Attractive and Repulsive Molecular Cues, and the Intermediate Role of Signaling Pathways.Neural plasticity · 2019Review
- Tissue Models for Neurogenesis and Repair in 3D.Advanced functional materials · 2018Article
- A microfluidic platform to study the effects of GDNF on neuronal axon entrapment.Journal of neuroscience methods · 2018Article
- CRISPR-Cas9 genome engineering: Treating inherited retinal degeneration.Progress in retinal and eye research · 2018Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The use of growth factors, such as glial cell line-derived neurotrophic factor (GDNF), for the treatment of peripheral nerve injury has been useful in promoting axon survival and regeneration. Unfortunately, finding a method that delivers the appropriate spatial and temporal release profile to promote functional recovery has proven difficult. Some release methods result in burst release profiles too short to remain effective over the regeneration period; however, prolonged exposure to GDNF can result in axonal entrapment at the site of release. Thus, GDNF was delivered in both a spatially and temporally controlled manner using a two-phase system comprised of an affinity-based release system and conditional lentiviral GDNF overexpression from Schwann cells (SCs). Briefly, SCs were transduced with a tetracycline-inducible (Tet-On) GDNF overexpressing lentivirus before transplantation. Three-centimeter acellular nerve allografts (ANAs) were modified by injection of a GDNF-releasing fibrin scaffold under the epineurium and then used to bridge a 3 cm sciatic nerve defect. To encourage growth past the ANA, GDNF-SCs were transplanted into the distal nerve and doxycycline was administered for 4, 6, or 8 weeks to determine the optimal duration of GDNF expression in the distal nerve. Live imaging and histomorphometric analysis determined that 6 weeks of doxycycline treatment resulted in enhanced regeneration compared to 4 or 8 weeks. This enhanced regeneration resulted in increased gastrocnemius and tibialis anterior muscle mass for animals receiving doxycycline for 6 weeks. The results of this study demonstrate that strategies providing spatial and temporal control of delivery can improve axonal regeneration and functional muscle reinnervation.
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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.