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In vitro differentiation of neural stem cells derived from human olfactory bulb into dopaminergic‐like neurons
Author(s) -
Alizadeh Rafieh,
Hassanzadeh Gholamreza,
Joghataei Mohammad Taghi,
Soleimani Mansoureh,
Moradi Fatemeh,
Mohammadpour Shahram,
Ghorbani Jahangir,
Safavi Ali,
Sarbishegi Maryam,
Pirhajati Mahabadi Vahid,
Alizadeh Leila,
Hadjighassem Mahmoudreza
Publication year - 2017
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.13504
Subject(s) - olfactory bulb , olfactory ensheathing glia , tyrosine hydroxylase , biology , neurogenesis , neural stem cell , microbiology and biotechnology , dopaminergic , stem cell , neuroscience , dopamine , central nervous system
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 ( NSC s) that are responsible for neurogenesis in the brain and the replacement of damaged cellular components throughout life. NSC s are capable of differentiating into neuronal and glial cells. We isolated NSC s 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 NSC s and proliferation markers were assessed. The multipotentiality of olfactory bulb NSC s was demonstrated by their capacity to differentiate into neurons, oligodendrocytes and astrocytes. To generate dopaminergic neurons, olfactory bulb NSC s 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 NSC s 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 NSC s as a promising cell‐based therapeutic strategy for Parkinson's disease.