Cell-based transplantation strategies are inherently combination therapies, as they may mediate spinal cord repair via trophic or phenotypic mechanisms. The growth factor expression profile and phenotype of transplanted cells are determined by the transplant population as well as by the site into which they are transplanted. Identifying the key pathways involved in transplant survival and differentiation, as well as neuroprotection and regeneration of endogenous tissue, will enable manipulation of both the transplanted cells and the microenvironment to improve transplant efficiency. High purity populations derived from stem cells will serve to better delineate lineage-specific mechanisms of repair, while providing both neurotrophic and phenotypic benefits to the injured spinal cord.