Optimization of trophic support for neural stem cell grafts in sites of spinal cord injury

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Abstract

Previously we utilized fibrin matrices and a cocktail of nine growth factors and a cell death inhibitor to promote survival and fill of neural stem cell (NSC) or neural progenitor cell (NPC) grafts to sites of spinal cord injury (SCI). In the current study, we examined whether the number of growth factors in a supportive matrix could be reduced to a more clinically practical number while retaining extensive NPC survival and fill of a spinal cord lesion site. NPCs derived from embryonic day 14 Fischer 344 rat spinal cords expressing green fluorescent protein (GFP) were embedded in fibrin matrices containing a defined growth factor cocktail: one to four factors were tested among nine different groups. Grafts were placed into C5 lateral hemisection lesion sites two weeks post-injury, and graft survival and fill was assessed two weeks later. We found that a four growth factor cocktail consisting of brain-derived neurotrophic factor (BDNF), basic-fibroblastic growth factor (bFGF), vascular endothelial growth factor (VEGF), and MDL28170, a cell death inhibitor, resulted in consistent graft survival, neuronal differentiation, and fill of the lesion site. Extensive stem cell-derived axonal outgrowth from the lesion site occurred, consistent with previous reports. Fewer than four growth factors resulted in suboptimal NPC fill of the lesion site. Collectively, these findings indicate that a simplified, four-component cocktail can support neural progenitor cell engraftment to a spinal cord lesion site to the same extent as a 10-component cocktail.

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