Abstract
IntroductionA growing number of studies have highlighted the potential of stem cell and more-differentiated neural cell transplantation as intriguing therapeutic approaches for neural repair after spinal cord injury (SCI).MethodsA conditionally immortalized neural stem cell line derived from human fetal spinal cord tissue (SPC-01) was used to treat a balloon-induced SCI. SPC-01 cells were implanted into the lesion 1 week after SCI. To determine the feasibility of tracking transplanted stem cells, a portion of the SPC-01 cells was labeled with poly-L-lysine-coated superparamagnetic iron-oxide nanoparticles, and the animals grafted with labeled cells underwent magnetic resonance imaging. Functional recovery was evaluated by using the BBB and plantar tests, and lesion morphology, endogenous axonal sprouting and graft survival, and differentiation were analyzed. Quantitative polymerase chain reaction (qPCR) was used to evaluate the effect of transplanted SPC-01 cells on endogenous regenerative processes.ResultsTransplanted animals displayed significant motor and sensory improvement 2 months after SCI, when the cells robustly survived in the lesion and partially filled the lesion cavity. qPCR revealed the increased expression of rat and human neurotrophin and motor neuron genes. The grafted cells were immunohistologically positive for glial fibrillary acidic protein (GFAP); however, we found 25% of the cells to be positive for Nkx6.1, an early motor neuron marker. Spared white matter and the robust sprouting of growth-associated protein 43 (GAP43)+ axons were found in the host tissue. Four months after SCI, the grafted cells matured into Islet2+ and choline acetyltransferase (ChAT)+ neurons, and the graft was grown through with endogenous neurons. Grafted cells labeled with poly-L-lysine-coated superparamagnetic nanoparticles before transplantation were detected in the lesion on T2-weighted images as hypointense spots that correlated with histologic staining for iron and the human mitochondrial marker MTCO2.ConclusionsThe transplantation of SPC-01 cells produced significant early functional improvement after SCI, suggesting an early neurotrophic action associated with long-term restoration of the host tissue, making the cells a promising candidate for future cell therapy in patients with SCI.
Highlights
A growing number of studies have highlighted the potential of stem cell and more-differentiated neural cell transplantation as intriguing therapeutic approaches for neural repair after spinal cord injury (SCI)
The current study addresses a previously unexplored issue in stem cell transplantation research for spinal cord repair in what are, to our knowledge, the first SCI experiments using a conditionally immortalized line of human fetal neural stem cells derived from the spinal cord (SPC-01)
FACS analysis of spinal precursor cell (SPC)-01 cells To characterize the expression of pluripotent and neural markers in human fetal neural stem cells from the SPC01 line, a series of FACS analyses was performed before transplantation
Summary
A growing number of studies have highlighted the potential of stem cell and more-differentiated neural cell transplantation as intriguing therapeutic approaches for neural repair after spinal cord injury (SCI). Pathologic changes after SCI are complex and include the interruption of ascending and descending pathways, the loss of neurons and glial cells, inflammation, scar formation, and demyelination [3,4] These events suggest a number of different steps required for SCI repair, such as minimizing progressive cell death and blocking scar formation; replacing lost cells and stimulating the injured cord to produce new cells; reconnecting injured nerve fibers with their original targets or with substitute targets; and maximizing the function of the spared nerve fibers by repairing their myelin sheaths. Celltransplantation therapies have become a major focus in preclinical research as a promising strategy for the treatment of SCI [5]
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