Dental pulp stem cells (DPSCs) are considered as an ideal stem cell source for the treatment of neurological diseases. In this study, we evaluated the therapeutic potency of DPSCs and brain-derived neurotrophic factor (BDNF) in focal cerebral ischemia using animal models. Following middle cerebral artery occlusion (MCAO), rats were randomized into four groups: the BDNF, DPSCs, DPSCs+BDNF and the controls injected with saline. DPSCs were transplanted and BDNF was injected into the DPSCs+BDNF group via the tail vein. The fate of the transplanted DPSCs in rat brains was evaluated using immunofluorescence, immunohistochemistry, western blot analysis and reverse transcription-polymerase chain reaction (RT-PCR). Adhesive removal tests and the modified neurological severity scores were used to estimate the restoration of neurological function. Proliferation of intravenously transplanted DPSCs was observed in the peripheral ischemic regions of the MCAO models. A green fluorescent dye PKH67 was used to label cells. PKH67-labeled DPSCs were co-localized with neuronal cell markers and 4′,6-diamidino-2-phenylindole (DAPI). DPSC transplantation combined with BDNF induced the expression of neural differentiation markers such as nestin, doublecortin (DCX) and neuronal specific filament (NF-H), suggesting that BDNF enhances the survival of DPSCs and differentiation into neuronal cells. Treatment with DPSCs combined with BDNF promoted the recovery of neurological function more effectively compared with BDNF injection or DPSC transplantation alone. In conclusion, treatment with DPSCs combined with BDNF enhances neurological recovery after stroke suggesting a novel therapeutic strategy against cerebral ischemia.

T helper 17 (Th17) cells are regarded as key factors in the pathogenesis of multiple sclerosis (MS). Although the involvement of certain microRNAs (miRNAs) in the development of MS has been reported, their roles in Th17 cell differentiation and MS pathogenesis remain elusive. In this study, we identified that let-7f-5p expression is significantly downregulated in CD4 + T cells from MS patients and during the process of Th17 differentiation. The overexpression of let-7f-5p suppressed Th17 differentiation, whereas the knockdown of let-7f-5p expression enhanced this progress. We then explored the molecular mechanism through which let-7f-5p suppressed Th17 differentiation and identified signal transducer and activator of transcription 3 (STAT3), a pivotal transcription factor of Th17 cells, as a direct target of let-7f-5p. In contrast to the downregulated expression of let-7f-5p, STAT3 and p-STAT3 protein levels were dramatically upregulated and inversely correlated with let-7f-5p in peripheral blood CD4 + T cells from MS patients. In conclusion, let-7f-5p functions as a potential inhibitor of Th17 differentiation in the pathogenesis of MS by targeting STAT3 and may serve as a new therapeutic target.

Background/Aims: Ischemic stroke is a major cause of disability and mortality worldwide, while effective restorative treatments are limited at present. Stem cell transplantation holds therapeutic potential for ischemic vascular diseases and may provide an opportunity for neural regeneration. Dental pulp stem cells (DPSCs) origin from neural crest and have neuro-ectodermal features including proliferation and multilineage differentiation potentials. Methods: The rat model of middle cerebral artery occlusion (MCAO) was used to evaluate whether intravenous administration of DPSCs can reduce infarct size and to estimate the migration and trans-differentiation into neuron-like cells in focal cerebral ischemia models. Brain tissues were collected at 4 weeks following cell transplantation and analyzed with immunofluorescence, immunohistochemistry and real-time polymerase chain reaction (RT-PCR) methods. Results: Intravenously administration of rat-derived DPSCs were found to migrate into the boundary of ischemic areas and expressed neural specific markers, reducing infarct volume and cerebral edema. Conclusions: These results suggest that DPSCs treatment may serve as a potential therapy for clinical stroke patients in the future.

Background Ischaemic stroke has become the main cause of death and severe neurological disorders, for which effective restorative treatments are currently limited. While stem cell transplantation offers therapeutic potential through neural regeneration, this approach is associated with the challenges of limited applicable sources. Hair follicle stem cells (HFSCs) are multipotential cells that can differentiate into ectodermal and mesodermal lineages and proliferate for long periods. The therapeutic potentials of HFSCs have not been investigated in ischaemic stroke models, and therefore, in this study, we aimed to determine whether they could survive and migrate to ischaemic areas after a stroke attack. Methods A rat model of middle cerebral artery ischaemia/reperfusion was established and intravenously administered HFSCs. The potential of HFSCs to migrate and differentiate into neuron-like cells as well as their ability to reduce the infarct size was evaluated. Rat brain tissue samples were collected 2 weeks after cell transplantation and analysed via TTC staining, immunofluorescence and immunohistochemistry methods. The data were statistically analysed and presented as the means ± standard deviations. Results Intravenously administrated rat HFSCs were able to migrate to the penumbra where they expressed neuron-specific markers, reduced the infarct volume and promoted neurological recovery. Conclusion HFSC transplantation has therapeutic potential for ischaemic stroke and is, therefore, worthy of further investigation toward possible clinical development for treating stroke patients.

Cirrhosis is the terminal stage of hepatic diseases and is prone to develop into hepatocyte carcinoma. Increasing evidence suggests that the transplantation of dental pulp stem cells (DPSCs) may promote recovery from cirrhosis, but the key regulatory mechanisms involved remain to be determined. In this study, we overexpressed human hepatocyte growth factor (hHGF) in primary rat DPSCs and evaluated the effects of HGF overexpression on the biological behaviors and therapeutic efficacy of grafted DPSCs in cirrhosis. Liver cirrhosis was induced via the intraperitoneal injection of CCl4 twice weekly for 12 weeks and was verified through histopathological and serological assays. HGF was overexpressed in DPSCs via transduction with a hHGF-lentiviral vector and confirmed based on the elevated expression and secretion of HGF. The HGF-overexpressing DPSCs were transplanted into rats intravenously. The HGF-overexpressing DPSCs showed increased survival and hepatogenic differentiation in host liver tissue at 6 weeks after grafting. They also exhibited a significantly greater repair potential in relation to cirrhosis pathology and impaired liver function than did DPSCs expressing HGF at physiological levels. Our study may provide an experimental basis for the development of novel methods for the treatment of liver cirrhosis in clinical practice.