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

Previously we reported that neural stem cells (NSCs) embedded in fibrin matrices containing 9 growth factors and an anti-apoptotic agent, survived and completely filled sites of spinal cord injury. In the current study, we examine whether the number of factors can be reduced while optimizing NSC survival and filling of the lesion site. NSCs derived from embryonic day 14 F344 rat spinal cord (expressing green fluorescent protein, GFP) were embedded in fibrin matrices containing a defined growth factor cocktail (1 to 4 factors among BDNF, bFGF, VEGF and calpain inhibitor, or original 10 factor combination). Grafts were made into a C5 lateral hemisection of wild-type adult F344 rats two weeks post-injury (N=3-6 per group, total 9 groups). Graft survival was assessed 2 weeks post-grafting. A 4 factor cocktail resulted in graft survival, neuronal differentiation, and filling of lesion site that was equivalent or superior to the 10 factor cocktail. The use of fewer than 4 growth factors, including single growth factors, also frequently but less consistently resulted in NSC survival and fill of lesion site. The effect of fewer growth factors on axon extension from the graft into the host cord is currently under analysis. Collectively, these findings suggest that excellent neural stem cell engraftment and survival can be achieved with a reduced growth factor cocktail, enhancing clinical practicality.

Society for Neuroscience: Chicago: Spinal Cord Injury: Therapeutic Strategies Trauma

Support: US Department of Veterans Affairs NIH the California Institute for Regenerative Medicine

Authors: J. ROBINSON1, L. GRAHAM1, D. WU1, Y. WANG1, M. TUSZYNSKI1,2, *P. P. LU1,2; 1UCSD, La Jolla, CA; 2VA-San Diego Healthcare Syst., San Diego, CA

Disclosures: J. Robinson: None. L. Graham: None. D. Wu: None. Y. Wang: None. Mark Tuszynski: None. Paul P. Lu: None.

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