Olfactory ectomesenchymal stem cells (OE-MSCs) possess the immunosuppressive activity and regeneration capacity and hold a lot of promises for neurodegenerative disorders treatment. This study aimed to determine OE-MSCs which are able to augment and differentiate into functional neurons and regenerate the CNS and also examine whether the implantation of OE-MSCs in the pars compacta of the substantia nigra (SNpc) can improve Parkinson's symptoms in a rat model-induced with 6-hydroxydopamine. We isolated OE-MSCs from lamina propria in olfactory mucosa and characterized them using flow cytometry and immunocytochemistry. The therapeutic potential of OE-MSCs was evaluated by the transplantation of isolated cells using a rat model of acute SN injury as a Parkinson's disease. Significant behavioral improvement in Parkinsonian rats was elicited by the OE-MSCs. The results demonstrate that the expression of PAX2, PAX5, PITX3, dopamine transporter, and tyrosine hydroxylase was increased by OE-MSCs compared to the control group which is analyzed with real-time polymerase chain reaction technique and immunohistochemical staining. In the outcome, the transplantation of 1,1′-dioctadecyl-3,3,3′3'-tetramethyl indocarbocyanine perchlorate labeled OE-MSCs that were fully differentiated to dopaminergic neurons contribute to a substantial improvement in patients with Parkinson's. Together, our results provide that using OE-MSCs in neurodegenerative disorders might lead to better neural regeneration.
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.
Background: Alzheimer's disease (AD) is a progressive cognitive disorder that is generally age-related. Although there has been great research focusing on this disease, there is still a lack of reliable therapeutic methods. Amyloid-β (Aβ) peptide has a critical function in neuropathology of AD. Stem cell therapy provides treatment by improving the neuronal system in neurodegenerative disorders. Human adipose-derived stem cells (hADSCs) are the most appropriate sources of stem cells due to their safety, high proliferative potential, and easy isolation. Objectives: The present study was designed to evaluate the histological and behavioral alterations after intravenous administration of hADSCs in the AD rat model. Methods: In this study, 32 male rats were used in four groups, as follows: control, sham, AD rat model, and hADSCs-treated group. We used Morris Water Maze (MWM) for evaluating behavioral changes and Nissl staining for determining the histological studies. Results: In this study, the AD model was confirmed by behavioral and histological analysis. Behavioral results showed that the spatial memory improved after hADSCs injection in the AD rat model while the time spent in the target quadrant was significantly higher in the hADSCs-treated group than in the AD rat model group. On the other hand, the number of dead cells significantly decreased in the hADSCs-treated group as analyzed by Nissl staining. Conclusions: Our findings revealed that hADSCs could transfer into the brain and improve memory and neuronal damage in the AD rat model.
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