title: Transplantation of primed or unprimed mouse embryonic stem cell-derived neural precursor cells improves cognitive function in Alzheimerian rats.
abstract: Alzheimer's disease (AD) is a neurodegenerative disorder that is characterized by progressive and irreversible decline of memory. Neuropathological features include the progressive degeneration of cholinergic neurons in the forebrain cholinergic projection system especially nucleus basalis of Meynert (nbM). New cell therapeutic approaches for the replacement of degenerated cells are being researched. The aim of this study was to investigate the production of cholinergic neurons from mouse embryonic stem cells (ESCs) and potential for utilizing ESC-derived neuronal precursor cells (NPCs) and primed NPCs (PNPCs) for cell restorative therapy in a rodent model of AD. NPCs were produced by growth factor-mediated selection under serum-free conditions and differentiated better into cholinergic neurons when NPCs primed with Shh (approximately 22%) in comparison with different cholinergic promoting factors. Behavioral assessment of unilateral nbM ibotenic acid-lesioned rats by Morris water maze and spatial probe test revealed a significant behavioral improvement in memory deficits following transplantation with NPCs and/or PNPCs. Immunohistochemical analysis revealed that the majority (approximately 70%) of the NPCs and/or PNPCs retained neuronal phenotype and approximately 40% of them had a cholinergic cell phenotype following transplantation with no tumor formation, indicating that these may be safe for transplantation. This experimental study has important implications as it suggests that the transplantation of mouse ESC-derived NPCs and/or following commitment to a cholinergic cell phenotype can promote behavioral recovery in a rodent model of AD.
authors.affiliation: Department of Cell and Molecular Biology, Royan Institute for Animal Biotechnology, Esfahan, Iran.
authors.forename: Farshad Homayouni
authors.initials: FH
authors.lastname: Moghadam
authors.forename: Hojatoallah
authors.initials: H
authors.lastname: Alaie
authors.forename: Khadije
authors.initials: K
authors.lastname: Karbalaie
authors.forename: Somayeh
authors.initials: S
authors.lastname: Tanhaei
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Nasr Esfahani
authors.forename: Hossein
authors.initials: H
authors.lastname: Baharvand
mesh_terms: D000544:Alzheimer Disease / Q000503:physiopathology / Q000601:surgery*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003071:Cognition / Q000502:physiology*; D053595:Embryonic Stem Cells / Q000637:transplantation*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D007051:Ibotenic Acid / Q000494:pharmacology; D053605:Leukemia Inhibitory Factor / Q000494:pharmacology; D008297:Male; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000637:transplantation*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D033581:Stem Cell Transplantation / Q000379:methods*
chemical_list: D018690:Excitatory Amino Acid Agonists; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D012333:RNA, Messenger; D007051:Ibotenic Acid