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.