Transplanted human fetal neural stem cells survive, migrate, and differentiate in ischemic rat cerebral cortex

TLDR

The study aims to characterize the survival, migration, and differentiation of human CNS stem cell‑derived neurospheres transplanted into the ischemic cortex of rats 7 days after distal MCA occlusion. Human neurospheres were transplanted into the ischemic cortex of rats 7 days after distal MCA occlusion to assess their survival, migration, and differentiation. Transplanted neurospheres survived robustly in both naive and ischemic brains 4 weeks post‑transplant, with survival higher near the lesion and inversely related to inflammatory cells; in ischemic rats they migrated up to ~1.2 mm toward the lesion, predominantly adopting neuronal phenotypes marked by doublecortin and β‑tubulin, while the microenvironment guided migration and fate.

Abstract

We characterize the survival, migration, and differentiation of human neurospheres derived from CNS stem cells transplanted into the ischemic cortex of rats 7 days after distal middle cerebral artery occlusion. Transplanted neurospheres survived robustly in naive and ischemic brains 4 wk posttransplant. Survival was influenced by proximity of the graft to the stroke lesion and was negatively correlated with the number of IB4-positive inflammatory cells. Targeted migration of the human cells was seen in ischemic animals, with many human cells migrating long distances (≈1.2 mm) predominantly toward the lesion; in naive rats, cells migrated radially from the injection site in smaller number and over shorter distances (0.2 mm). The majority of migrating cells in ischemic rats had a neuronal phenotype. Migrating cells between the graft and the lesion expressed the neuroblast marker doublecortin, whereas human cells at the lesion border expressed the immature neuronal marker β-tubulin, although a small percentage of cells at the lesion border also expressed glial fibrillary acid protein (GFAP). Thus, transplanted human CNS (hCNS)-derived neurospheres survived robustly in naive and ischemic brains, and the microenvironment influenced their migration and fate.