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1.
Tissue Cell ; 73: 101649, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34583247

ABSTRACT

Various methods have been used to induce the neuronal differentiation of marrow mesenchymal stem cells (MSCs). However, the limited induction efficiency of cells in vitro has restricted their use. Therefore, identifying a simple and efficient treatment method is necessary. Dendrobium officinale is an important traditional Chinese medicine, and its main component, polysaccharides, has many pharmacological activities. However, the effects of D. officinale polysaccharide (DOP) on the neuronal differentiation of bone marrow mesenchymal stem cells (BMSCs) and treatment of ischaemic stroke remain unknown. We found that DOP promoted the neuronal differentiation of BMSCs by increasing the expression levels of neural markers, and the optimal concentration of DOP was 25 µg/mL. Additionally, the Notch signalling pathway was inhibited during the neuronal differentiation of BMSCs induced by DOP, and this effect was strengthened using an inhibitor of this pathway. The Wnt signalling pathway was activated during the differentiation of BMSCs, and inhibition of the Wnt signalling pathway downregulated the expression of neuronal genes. Furthermore, the transplantation of neuron-like cells induced by DOP improved neuronal recovery, as the brain infarct volume, neurologic severity scores and levels of inflammatory factors were all significantly reduced in vivo. In conclusion, DOP is an effective inducer of the neuronal differentiation of BMSCs and treatment option for ischaemic stroke.


Subject(s)
Dendrobium/chemistry , Mesenchymal Stem Cells/cytology , Neurons/cytology , Polysaccharides/pharmacology , Recovery of Function , Stroke/physiopathology , Stroke/therapy , Animals , Biomarkers/metabolism , Cell Differentiation/drug effects , Cell Shape/drug effects , Cerebral Ventricles/pathology , Disease Models, Animal , Infarction, Middle Cerebral Artery/complications , Male , Neurons/drug effects , Rats, Sprague-Dawley , Receptors, Notch/metabolism , Recovery of Function/drug effects , Wnt Signaling Pathway/drug effects
2.
Tissue Cell ; 69: 101482, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33418236

ABSTRACT

Ischemia or hemorrhagic stroke is one of the leading causes of death and permanent disability in the worldwide population. As a consequence of the potential increasing in stroke, stem cell therapy is currently an area of intense focus. However, there are less data available regarding the promotion of healing efficacy after stroke. The present study aimed to investigate whether the cytokine interleukin-17A (IL-17A) could have a role in promoting the neuronal differentiation of mesenchymal stem cells (MSCs) and to investigate the associated molecular mechanism. Firstly, different concentration of IL-17A at range from 5-40 ng/mL was applied to stimulate bone marrow MSCs (BMSCs) during the course of neurogenic differentiation. Then reverse transcription-PCR, histological analyses and immunofluorescence assays were used to determine the optimum concentration of IL-17A in promoting the neuronal differentiation of BMSCs, which was 20 ng/mL. Mechanistically, Wnt signaling pathway was activated and Notch signaling pathway was suppressed. In addition, there were antergic effect of these two signaling pathways modulating the neurogenic differentiation of BMSCs induced by IL-17A. The present study demonstrated the potential role of IL-17A-based BMSCs strategy for promoting neuronal differentiation in vitro. However, the treatment efficacy could be considerably confirmed in animals with ischemia stroke. Therefore, a more sophisticated strategy that addresses the complicated treatment associated with stroke is needed.


Subject(s)
Cell Differentiation , Interleukin-17/pharmacology , Mesenchymal Stem Cells/cytology , Neurons/cytology , Animals , Biomarkers/metabolism , Cell Differentiation/drug effects , Cell Shape/drug effects , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/metabolism , Models, Biological , Neurons/drug effects , Neurons/metabolism , Rats, Sprague-Dawley , Receptors, Notch/metabolism , Wnt Signaling Pathway/drug effects
3.
Acta Biochim Biophys Sin (Shanghai) ; 52(9): 1016-1029, 2020 Sep 08.
Article in English | MEDLINE | ID: mdl-32845287

ABSTRACT

Recent studies have reported an increasing incidence of ischemic stroke, particularly in younger age groups. Dental pulp stem cells (DPSCs) and periodontal ligament stem cells (PDLSCs) are the most common stem cells acquired from the teeth of adults, even elderly people. However, there are no detailed reports on whether DPSCs or PDLSCs are suitable for the treatment of ischemic stroke. In this study, the in vitro differentiation of DPSCs and PDLSCs into neuron-like cells was evaluated. Then, we established a rat model of cerebral ischemia. DPSCs or PDLSCs were administered to animals, and the therapeutic effects of these two types of cells were investigated. The results showed that PDLSCs had a higher differentiation rate than DPSCs. Immunofluorescence studies showed that the expression of the neuronal differentiation marker Thy-1 was higher in PDLSCs than in DPSCs, and other gene markers of neuronal differentiation showed corresponding trends, which were confirmed by western blot analysis. In this process, the Notch and Wnt signaling pathways were inhibited and activated, respectively. Finally, rats with transient occlusion of the right middle cerebral artery were used as a model to assess the therapeutic effect of PDLSCs and DPSCs on ischemia. The results showed that rats in the PDLSC-treated group emitted significantly greater red fluorescence signal than the DPSC-treated group. PDLSC transplantation promoted the recovery of neurological function more effectively than DPSC transplantation. Hence, PDLSCs represent an autogenous source of adult mesenchymal stem cells with desirable biological properties and may be an ideal candidate for clinical applications.


Subject(s)
Brain Ischemia , Cell Differentiation , Dental Pulp/metabolism , Neurons/metabolism , Periodontal Ligament/metabolism , Stem Cell Transplantation , Stem Cells/metabolism , Animals , Brain Ischemia/metabolism , Brain Ischemia/pathology , Brain Ischemia/therapy , Dental Pulp/pathology , Disease Models, Animal , Heterografts , Humans , Male , Neurons/pathology , Periodontal Ligament/pathology , Rats , Rats, Sprague-Dawley , Stem Cells/pathology
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