title: In vitro differentiation of neural stem cells derived from human olfactory bulb into dopaminergic-like neurons.
abstract: This study describes a new accessible source of neuronal stem cells that can be used in Parkinson's disease cell transplant. The human olfactory bulb contains neural stem cells (NSCs) that are responsible for neurogenesis in the brain and the replacement of damaged cellular components throughout life. NSCs are capable of differentiating into neuronal and glial cells. We isolated NSCs from the olfactory bulb of brain-death donors and differentiated them into dopaminergic neurons. The olfactory bulb tissues obtained were cultured in Dulbecco's modified Eagle's medium/nutrient mixture F12, B27 supplemented with basic fibroblast growth factor, epidermal growth factor and leukemia inhibitory factor. The NSCs and proliferation markers were assessed. The multipotentiality of olfactory bulb NSCs was demonstrated by their capacity to differentiate into neurons, oligodendrocytes and astrocytes. To generate dopaminergic neurons, olfactory bulb NSCs were differentiated in neurobasal medium, supplemented with B27, and treated with sonic hedgehog, fibroblast growth factor 8 and glial cell-derived neurotrophic factor from the 7th to the 21st day, followed by detection of dopaminergic neuronal markers including tyrosine hydroxylase and aromatic l-amino acid decarboxylase. The cells were expanded, established in continuous cell lines and differentiated into the two classical neuronal phenotypes. The percentage of co-positive cells (microtubule-associated protein 2 and tyrosine hydroxylase; aromatic l-amino acid decarboxylase and tyrosine hydroxylase) in the treated cells was significantly higher than in the untreated cells. These results illustrate the existence of multipotent NSCs in the adult human olfactory bulb that are capable of differentiating toward putative dopaminergic neurons in the presence of trophic factors. Taken together, our data encourage further investigations of the possible use of olfactory bulb NSCs as a promising cell-based therapeutic strategy for Parkinson's disease.
authors.affiliation: Cellular and Molecular Research Center, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.|ENT and Head & Neck Research Center and Department, Hazrat Rasoul Akram Hospital, Iran University of Medical Sciences (IUMS), Tehran, Iran.
authors.forename: Rafieh
authors.initials: R
authors.lastname: Alizadeh
authors.affiliation: Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Gholamreza
authors.initials: G
authors.lastname: Hassanzadeh
authors.affiliation: Cellular and Molecular Research Center, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.|Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad Taghi
authors.initials: MT
authors.lastname: Joghataei
authors.affiliation: Cellular and Molecular Research Center, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.|Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Mansoureh
authors.initials: M
authors.lastname: Soleimani
authors.affiliation: Cellular and Molecular Research Center, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.|Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Moradi
authors.affiliation: Cellular and Molecular Research Center, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.|Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.|Department of Anatomy, School of Medicine, Ilam University of Medical Sciences, Ilam, Iran.
authors.forename: Shahram
authors.initials: S
authors.lastname: Mohammadpour
authors.affiliation: Organ Procurement and Transplant Unit (OPTU), Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Jahangir
authors.initials: J
authors.lastname: Ghorbani
authors.affiliation: Organ Procurement and Transplant Unit (OPTU), Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Safavi
authors.affiliation: Department of Anatomy, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Sarbishegi
authors.affiliation: ENT and Head & Neck Research Center and Department, Hazrat Rasoul Akram Hospital, Iran University of Medical Sciences (IUMS), Tehran, Iran.|Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Vahid
authors.initials: V
authors.lastname: Pirhajati Mahabadi
authors.affiliation: Shefa Neuroscience Research Center, Khatam-Alanbia Hospital, Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran, Iran.
authors.forename: Leila
authors.initials: L
authors.lastname: Alizadeh
authors.affiliation: Brain and Spinal Cord Injury Research Center, Imam Khomeinin Hospital, Blv Keshavarz, Tehran University of Medical Sciences, Tehran, 1419733141, Iran.|School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mahmoudreza
authors.identifier: 0000-0002-3132-9904
authors.initials: M
authors.lastname: Hadjighassem
mesh_terms: D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism; D002478:Cells, Cultured; D059290:Dopaminergic Neurons / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D008297:Male; D058953:Neural Stem Cells / Q000166:cytology*; D055495:Neurogenesis; D009830:Olfactory Bulb / Q000166:cytology*; D009836:Oligodendroglia / Q000166:cytology; D051381:Rats; D017208:Rats, Wistar; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D014446:Tyrosine 3-Monooxygenase; D001142:Aromatic-L-Amino-Acid Decarboxylases
keywords: dopaminergic neurons; human olfactory bulb; in vitro differentiation; neural stem cell