title: Human olfactory bulb neural stem cells expressing hNGF restore cognitive deficit in Alzheimer's disease rat model.
abstract: In this study, we aim to demonstrate the fate of allogenic adult human olfactory bulb neural stem/progenitor cells (OBNSC/NPCs) transplanted into the rat hippocampus treated with ibotenic acid (IBO), a neurotoxicant specific to hippocampal cholinergic neurons that are lost in Alzheimer's disease. We assessed their possible ability to survive, integrate, proliferate, and differentiate into different neuronal and glial elements: we also evaluate their possible therapeutic potential, and the mechanism(s) relevant to neuroprotection following their engraftment into the CNS milieu. OBNSC/NPCs were isolated from adult human olfactory bulb patients, genetically engineered to express GFP and human nerve growth factor (hNGF) by lentivirus-mediated infection, and stereotaxically transplanted into the hippocampus of IBO-treated animals and controls. Stereological analysis of engrafted OBNSCs eight weeks post transplantation revealed a 1.89 fold increase with respect to the initial cell population, indicating a marked ability for survival and proliferation. In addition, 54.71 ± 11.38%, 30.18 ± 6.00%, and 15.09 ± 5.38% of engrafted OBNSCs were identified by morphological criteria suggestive of mature neurons, oligodendrocytes and astrocytes respectively. Taken together, this work demonstrated that human OBNSCs expressing NGF ameliorate the cognitive deficiencies associated with IBO-induced lesions in AD model rats, and the improvement can probably be attributed primarily to neuronal and glial cell replacement as well as the trophic influence exerted by the secreted NGF.
authors.affiliation: Department of Cytology and Histology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt.
authors.forename: Hany E S
authors.initials: HE
authors.lastname: Marei
authors.forename: Amany
authors.initials: A
authors.lastname: Farag
authors.forename: Asma
authors.initials: A
authors.lastname: Althani
authors.forename: Nahla
authors.initials: N
authors.lastname: Afifi
authors.forename: Ahmed
authors.initials: A
authors.lastname: Abd-Elmaksoud
authors.forename: Samah
authors.initials: S
authors.lastname: Lashen
authors.forename: Shaymaa
authors.initials: S
authors.lastname: Rezk
authors.forename: Roberto
authors.initials: R
authors.lastname: Pallini
authors.forename: Patrizia
authors.initials: P
authors.lastname: Casalbore
authors.forename: Carlo
authors.initials: C
authors.lastname: Cenciarelli
mesh_terms: D000544:Alzheimer Disease / Q000628:therapy*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D064987:Cell- and Tissue-Based Therapy; D059329:Cholinergic Neurons / Q000187:drug effects; D003072:Cognition Disorders / Q000628:therapy; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D057809:HEK293 Cells; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D007051:Ibotenic Acid / Q000494:pharmacology; D008297:Male; D018782:Maze Learning; D018919:Neovascularization, Physiologic; D020932:Nerve Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D058953:Neural Stem Cells / Q000378:metabolism / Q000637:transplantation*; D009830:Olfactory Bulb / Q000166:cytology*; D009836:Oligodendroglia / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D049452:Green Fluorescent Proteins; D007051:Ibotenic Acid; D020932:Nerve Growth Factor