Transplantation of glial-restricted precursor cells into the adult spinal cord: survival, glial-specific differentiation, and preferential migration in white matter.

Abstract

Glial-restricted precursor (GRP) cells are among a number of candidate cells for transplantation repair of CNS injury. The isolation and characterization of these cells in vitro have been described previously, but their in vivo properties are not well understood. We examined the fate and migration of grafted fetal GRP cells harvested from alkaline phosphatase-expressing transgenic rats into intact and injured spinal cord. Transplanted GRP cells survived for at least 6 weeks and differentiated along astrocytic and oligodendrocytic but not neuronal lineages. Cells grafted into the intact spinal cord exhibited robust migration along longitudinal white matter tracts and by 6 weeks migrated more than 15 mm. In contrast, migration of GRP cells in the gray matter was very limited. We then examined the phenotypic properties of proliferating endogenous precursors in response to injury by BrdU labeling. The predominant proliferating population seen after injury consisted of GRP-like cells with Nkx2.2/olig2 phenotype. Incorporation of BrdU by endogenous cells suggests that the environment provides proliferation signals and is permissive to glial precursor survival. To test if exogenous GRP cells would respond similarly, we transplanted GRP cells into a lateral funiculus injury. GRP cells survived and differentiated along glial lineages and migrated along white matter tracts in the injured spinal cord. Directed homing toward the lesion was not seen and there was no significant bias in differentiation between cells transplanted into injured and uninjured spinal cord. GRP cell transplants may therefore provide a cellular transplant that can respond to appropriate endogenous cues to produce therapeutic molecules and new glial cells after injury.