Embryonic stem cell-derived neural precursor cells improve memory dysfunction in Aβ(1-40) injured rats

The versatility of neural precursor cells (NPCs) derived from mouse embryonic stem cells (ESCs) has recently rekindled interests in cell replacement strategies aimed at neurodegenerative diseases. We observed the survival, migration, differentiation and functional recovery of NPCs transplanted into the hippocampus of aggregated beta-amyloid (A beta) peptide injured rats. Congo Red plaques, Fluro-jade B positive degenerating neurons and neuronal loss were observed in the A beta-injured hippocampus of rats, accompanied with significant increases in escape latency and decrease in the ratio of exploratory time in a Morris water maze test. EGFP-expressing mouse ES cells were induced into Nestin-positive NPCs before transplantation into the A beta-injured hippocampus. A marked decrease in escape latency and exploratory time were observed at least 16 weeks after transplantation compared to A beta-injured animals without grafts. Grafted EGFP-expressing NPCs spread away from the injection tract and about 12.01 +/- 0.67% and 9.41 +/- 0.78% of NPCs differentiated into, respectively, GFAP- and NF200-positive cells 4 W after transplantation. These ratios gradually increased to 40.25 +/- 0.57% and 19.35 +/- 0.84% by 16 W. The restoration of hippocampal function by ESCs suggests that cell transplantation may be the effective choice to improve the cognitive function caused by A beta injured. (C) 2008 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.