Embryonic stem cell-derived neural precursor cells improve memory dysfunction in Abeta(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 (Abeta) peptide injured rats. Congo Red plaques, Fluro-jade B positive degenerating neurons and neuronal loss were observed in the Abeta-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 Abeta-injured hippocampus. A marked decrease in escape latency and exploratory time were observed at least 16 weeks after transplantation compared to Abeta-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 Abeta injured.
Tang
Jun
J
Department of Physiology, Third Military Medical University, 30 Gaotanyan Street, Chongqing 400038, PR China.
Xu
Haiwei
H
Fan
Xiaotang
X
Li
Dabing
D
Rancourt
Derrick
D
Zhou
Guangji
G
Li
Zhifang
Z
Yang
Li
L
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D001927:Brain Diseases / Q000209:etiology / Q000601:surgery*; D002454:Cell Differentiation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000637:transplantation*; D005434:Flow Cytometry; D006085:Graft Survival; D006624:Hippocampus / Q000473:pathology / Q000601:surgery; D007150:Immunohistochemistry; D008297:Male; D018782:Maze Learning; D008569:Memory Disorders / Q000209:etiology / Q000601:surgery*; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000637:transplantation*; D051381:Rats; D017208:Rats, Wistar; D033581:Stem Cell Transplantation
D016229:Amyloid beta-Peptides