Endogenous repair mechanisms after human stem cell transplantation following stroke

Abstract

Stem cell transplantation has emerged as a promising new experimental treatment for stroke; understanding its mechanism of action will facilitate the translation of stem cell therapy to the clinic. The ultimate change in brain plasticity is manifested at the synaptic level, however, the synaptic remodeling after stem cell therapy remains unknown. Vehicle or human neural progenitor cells (hNPCs) derived from fetal cortex were transplanted into the ischemic cortex of Nude rats at 7 days after distal middle cerebral artery occlusion. Transplantation of hNPCs significantly improved behavioral recovery after stroke compared to vehicle-treated rats at 3–4 weeks post-transplantation. We found that transplanted stem cells enhanced endogenous brain repair processes including structural brain plasticity. hNPC-treated rats had a higher density of glutamatergic synapses in layer 5 at 4 weeks posttransplantation, compared to vehicle-treated rats. These results provide novel new information about the organization of synaptic circuitry and its plasticity after stem cell therapy. These data suggest that stem cells alter the synaptic remodeling of glutamatergic synapses after stroke and this is coincident with stem cell-induced functional recovery.