Differential effects of distinct central nervous system regions on cell migration and axonal extension of neural precursor transplants

Abstract

Transplantation of neural precursor cells (NPCs) is a promising therapeutic strategy in CNS injury. However, the adult CNS lacks instructive signals present during development and, depending on the region and type of transplant, may be inhibitory for neuron generation and axonal growth. We examined the effects of the white matter in different regions of the adult CNS on the properties of NPC transplants with respect to cell survival, differentiation, migration, and axonal growth. NPCs were prepared from day 13.5 embryonic spinal cord of transgenic rats that express the human placental alkaline phosphatase (AP) reporter. These NPCs were injected unilaterally into the cervical spinal cord white matter and into the corpus callosum of adult rats and were analyzed immunohistochemically 2 weeks later. NPCs survived in both regions and differentiated into astrocytes, oligodendrocytes, and neurons, with no apparent differences in survival or phenotypic composition. However, in the spinal cord white matter, graft-derived cells, identified as precursors and glial cells, migrated from the injection site rostrally and caudally, whereas, in the corpus callosum, graft-derived cells did not migrate and remained at the injection site. Importantly, graft-derived neurons extended axons from the grafting site along the corpus callosum past the midline, entering into the contralateral side of the corpus callosum. These results demonstrate dramatic differences between white matter regions in the spinal cord and brain with respect to cell migration and axonal growth and underscore the importance of considering the effects of the local CNS environment in the design of effective transplantation strategies.