UC San Diego

Neural stem cells (NSCs) can differentiate into both neurons and glia after transplantation into sites of spinal cord injury (SCI). The neuronal component of stem cell grafts has the potential to form functional synaptic relays across the lesion site. The glial component, on the other hand, may reform a blood–spinal cord barrier (BSCB), support neuronal function, and potentially contribute to remyelination. We performed a long-term, time-course study for 1.5 years focused on astrocyte survival, migration, differentiation, integration, and safety following transplantation of human NSCs into sites of C5 hemisection in immunodeficient rats. Subjects were sacrificed at 1, 3, 6, 12, and 18 months after transplantation.

Notably, NSCs that adopted a neuronal fate did not migrate from the lesion site. In contrast, transplanted cells that adopted astrocyte fates exhibited long-distance migration from the lesion site and through host white matter in rostrocaudal directions. NSCs migrated from the lesion slowly, at a mean rate of 2-3 mm per month, divided as they migrated, and gradually differentiated into astrocytes. After 1.5 years, astrocytes migrated 9 spinal cord segments, caudally to the mid-thoracic level, and rostrally into the brainstem. The migrated human astrocytes joined the endogenous population of astrocytes in the host spinal cord, extended endfeet towards cellular constituents of the blood-spinal cord barrier, and formed perivascular astrocytic networks connected by gap junctions, suggesting structural and potentially functional integration. No adverse consequences of this extended glial migration were detected. Thus, human astrocytes can migrate from NSC grafts transplanted into sites of SCI and safely integrate into the host central nervous system.