Spinal cord injury (SCI) causes axonal damage and demyelination, neural cell death, and comprehensive tissue loss, resulting in devastating neurological dysfunction. Neural stem/progenitor cell (NSPCs) transplantation provides therapeutic benefits for neural repair in SCI, and glial cell linederived neurotrophic factor (GDNF) has been uncovered to have capability of stimulating axonal regeneration and remyelination after SCI. In this study, to evaluate whether GDNF would augment therapeutic effects of NSPCs for SCI, GDNF-encoding or mock adenoviral vector-transduced human NSPCs (GDNF-or Mock-hNSPCs) were transplanted into the injured thoracic spinal cords of rats at 7 days after SCI. Grafted GDNFhNSPCs showed robust engraftment, long-term survival, an extensive distribution, and increased differentiation into neurons and oligodendroglial cells. Compared with Mock-hNSPC- and vehicle-injected groups, transplantation of GDNF-hNSPCs significantly reduced lesion volume and glial scar formation, promoted neurite outgrowth, axonal regeneration and myelination, increased Schwann cell migration that contributed to the myelin repair, and improved locomotor recovery. In addition, tract tracing demonstrated that transplantation of GDNF-hNSPCs reduced significantly axonal dieback of the dorsal corticospinal tract (dCST), and increased the levels of dCST collaterals, propriospinal neurons (PSNs), and contacts between dCST collaterals and PSNs in the cervical enlargement over that of the controls. Finally grafted GDNF-hNSPCs substantially reversed the increased expression of voltage-gated sodium channels and neuropeptide Y, and elevated expression of GABA in the injured spinal cord, which are involved in the attenuation of neuropathic pain after SCI. These findings suggest that implantation of GDNF-hNSPCs enhances therapeutic efficiency of hNSPCs-based cell therapy for SCI.
Keywords: Cell-based therapy; Glial cell line-derived neurotrophic factor; Mechanical allodynia; Neural stem/progenitor cells; Paraplegia; Spinal cord injuries.
Glial Cell Line-Derived Neurotrophic Factor-Enriched Bridging Transplants Promote Propriospinal Axonal Regeneration and Enhance Myelination After Spinal Cord InjuryC Iannotti et al. Exp Neurol 183 (2), 379-93. PMID 14552879.Glial cell line-derived neurotrophic factor (GDNF), a distant member of the transforming growth factor-beta (TGF-beta) family, is widely expressed in the developing and a …
Pain With No Gain: Allodynia Following Neural Stem Cell Transplantation in Spinal Cord InjuryMY Macias et al. Exp Neurol 201 (2), 335-48. PMID 16839548.Transplantation of neural stem cells (NSCs) in the injured spinal cord has been shown to improve functional outcome; however, recent evidence has demonstrated forelimb al …
Suppression of MicroRNA-383 Enhances Therapeutic Potential of Human Bone-Marrow-Derived Mesenchymal Stem Cells in Treating Spinal Cord Injury via GDNFGJ Wei et al. Cell Physiol Biochem 41 (4), 1435-1444. PMID 28365701.Suppression of miR-383 may increase the therapeutic potential of human bone-marrow-derived MSCs in treating SCI via augmentation of GDNF protein levels.
History of Glial Cell Line-Derived Neurotrophic Factor (GDNF) and Its Use for Spinal Cord Injury RepairMJ Walker et al. Brain Sci 8 (6). PMID 29899247. - ReviewFollowing an initial mechanical insult, traumatic spinal cord injury (SCI) induces a secondary wave of injury, resulting in a toxic lesion environment inhibitory to axona …
Stem Cell-Based Cell Therapy for Spinal Cord InjuryBG Kim et al. Cell Transplant 16 (4), 355-64. PMID 17658126. - ReviewTraumatic injuries to the spinal cord lead to severe and permanent neurological deficits. Although no effective therapeutic option is currently available, recent animal s …