Differentiation of human olfactory system‐derived stem cells into dopaminergic neuron‐like cells: A comparison between olfactory bulb and mucosa as two sources of stem cells

Abstract

Cell transplantation has become a possible therapeutic approach in the treatment of neurodegenerative diseases of the nervous system by replacing lost cells. The current study aimed to make a comparison between the differentiation capacity of the olfactory bulb neural stem cells (OB-NSCs) and olfactory ectomesenchymal stem cells (OE-MSCs) into dopaminergic-like neurons under the inductive effect of transforming growth factor β (TGF-β).After culturing and treating with TGF-β, the differentiation capacities of both types of stem cells into dopaminergic neuron-like cells were evaluated.Quantitative real-time polymerase chain reaction analysis 3 weeks after induction demonstrated that the mRNA expression of the dopaminergic activity markers tyrosine hydroxylase (TH), dopamine transporter (DAT), paired box gene 2 (PAX2), and PAX5 in the neuron-like cells derived from OB-NSCs was significantly higher than those derived from OE-MSCs. These findings were further supported by the immunocytochemistry staining showing that the expression of the tyrosine hydroxylase, DAT, PAX2, and paired like homeodomain 3 seemed to be slightly higher in OB-NSCs compared with OE-MSCs.Despite the lower differentiation capacity of OE-MSCs, other considerations such as a noninvasive and easier harvesting process, faster proliferation attributes, longer life span, autologous transplantability, and also the easier and inexpensive cultural process of the OE-MSCs, cumulatively make these cells the more appropriate alternative in the case of autologous transplantation during the treatment process of neurodegenerative disorders like Parkinson's disease. K E Y W O R D Sdopaminergic neurons, ectomesenchymal stem cells, neural stem cells, olfactory bulb, olfactory mucosa Rafieh Alizadeh and Farnaz Ramezanpour contributed equally to this work.

Functional dopaminergic neurons derived from human chorionic mesenchymal stem cells ameliorate striatal atrophy and improve behavioral deficits in Parkinsonian rat model

“…The antibodies were against β‐tubulin3 (ABCAM) and TH (ABCAM). The cells were washed with PBS, incubated with TRITC/FITC‐conjugated secondary antibody (ABCAM), for 60 min and eventually, immunoreactive cells were observed, using fluorescence microscopy (Alizadeh et al, ).…”

Why is olfactory neuroepithelium?

“…Additionally, a study showed that in vitro ONs cultured in a special medium possess characteristics of photoreceptor cells [84]. More studies showed that human olfactory systemderived stem cells differentiating and proliferating into dopaminergic neuron-like cells in a special culture medium [85][86][87]. In experimental studies, transplanting olfactory mucosa stem cells in Parkinson's animal models found cells with dopaminergic neuron markers in different brain areas [88,89].…”

Illuminating and Sniffing Out the Neuromodulatory Roles of Dopamine in the Retina and Olfactory Bulb

“…These dopamine neurons, subtypes of PGCs and GCs, are continuously generated in the subventricular zone (SVZ) and migrate to the OB throughout adulthood (McLean and Shipley, 1988;Gross, 2000;Lledo et al, 2006;Merkle et al, 2007;Whitman and Greer, 2007;Pignatelli et al, 2009;Galliano et al, 2018). The implication of these adult-born neurons is that they could be used as therapeutic treatment for PD (Baker et al, 2001;Alizadeh et al, 2019).…”