Human Olfactory Bulb Neural Stem Cells expressing hNGF Restore Cognitive Deficit in Alzheimer's Disease Rat Model

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 neuronsthat are lost in Alzheimer's disease. We assessed their possible ability to survive, integrate, proliferate, and differentiate into differentneuronal and glial elements: we also evaluate their possible therapeutic potential, and the mechanism(s) relevant to neuroprotectionfollowing their engraftment into the CNS milieu. OBNSC/NPCs were isolated from adult human olfactory bulb patients, geneticallyengineered to express GFP and human nerve growth factor (hNGF) by lentivirus-mediated infection, and stereotaxically transplanted intothe hippocampus of IBO-treated animals and controls. Stereological analysis of engrafted OBNSCs eight weeks post-transplantationrevealed 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 matureneurons, oligodendrocytes and astrocytes respectively. Taken together, this work demonstrated that human OBNSCs expressing NGFameliorate the cognitive deficiencies associated with IBO-induced lesions in AD model rats, and the improvement can probably beattributed primarily to neuronal and glial cell replacement as well as the trophic influence exerted by the secreted NGF.