Although human amnion derived mesenchymal stem cells (AMSC) are a promising source of stem cells, their therapeutic potential for traumatic brain injury (TBI) has not been widely investigated. In this study, we evaluated the therapeutic potential of AMSC using a rat TBI model. AMSC were isolated from human amniotic membrane and characterized by flow cytometry. After induction, AMSC differentiated in vitro into neural stem-like cells (AM-NSC) that expressed higher levels of the neural stem cell markers, nestin, sox2 and musashi, in comparison to undifferentiated AMSC. Interestingly, the neurotrophic factors, brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin 3 (NT-3), glial cell derived neurotrophic factor (GDNF) and ciliary neurotrophic factor (CNTF) were markedly upregulated after neural stem cell induction. Following transplantation in a rat TBI model, significant improvements in neurological function, brain tissue morphology, and higher levels of BDNF, NGF, NT-3, GDNF and CNTF, were observed in the AM-NSC group compared with the AMSC and Matrigel groups. However, few grafted cells survived with minimal differentiation into neural-like cells. Together, our results suggest that transplantation of AM-NSC promotes functional rehabilitation of rats with TBI, with enhanced expression of neurotrophic factors a likely mechanistic pathway.

Human amniotic membrane mesenchymal stem cells (hAMSCs) are considered ideal candidate stem cells for cell-based therapy. In this study, we assessed whether hAMSCs transplantation promotes neurological functional recovery in rats after traumatic spinal cord injury (SCI). In addition, the potential mechanisms underlying the possible benefits of this therapy were investigated. Female Sprague-Dawley rats were subjected to SCI using a weight drop device and then hAMSCs, or phosphate-buffered saline (PBS) were immediately injected into the contused dorsal spinal cord at 2 mm rostral and 2 mm caudal to the injury site. Our results indicated that transplanted hAMSCs migrated in the host spinal cord without differentiating into neuronal or glial cells. Compared with the control group, hAMSCs transplantation significantly decreased the numbers of ED1 macrophages/microglia and caspase-3 cells. In addition, hAMSCs transplantation significantly increased the levels of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) in the injured spinal cord, and promoted both angiogenesis and axonal regeneration. These effects were associated with significantly improved neurobehavioral recovery in the hAMSCs transplantation group. These results show that transplantation of hAMSCs provides neuroprotective effects in rats after SCI, and could be candidate stem cells for the treatment of SCI.

No abstract

PRMT6, a type I arginine methyltransferase, di-methylates the arginine residues of both histones and non-histones asymmetrically. Increasing evidence indicates that PRMT6 plays a tumor mediator involved in human malignancies. Here, we aim to uncover the essential role and underlying mechanisms of PRMT6 in promoting glioblastoma (GBM) proliferation. Investigation of PRMT6 expression in glioma tissues demonstrated that PRMT6 is overexpressed, and elevated expression of PRMT6 is negatively correlated with poor prognosis in glioma/GBM patients. Silencing PRMT6 inhibited GBM cell proliferation and induced cell cycle arrest at the G0/G1 phase, while overexpressing PRMT6 had opposite results. Further, we found that PRMT6 attenuates the protein stability of CDKN1B by promoting its degradation. Subsequent mechanistic investigations showed that PRMT6 maintains the transcription of CDC20 by activating histone methylation mark (H3R2me2a), and CDC20 interacts with and destabilizes CDKN1B. Rescue experimental results confirmed that PRMT6 promotes the ubiquitinated degradation of CDKN1B and cell proliferation via CDC20. We also verified that the PRMT6 inhibitor (EPZ020411) could attenuate the proliferative effect of GBM cells. Our findings illustrate that PRMT6, an epigenetic mediator, promotes CDC20 transcription via H3R2me2a to mediate the degradation of CDKN1B to facilitate GBM progression. Targeting PRMT6-CDC20-CDKN1B axis might be a promising therapeutic strategy for GBM.

Transplantation of human amniotic mesenchymal stem cells (hAM-MSCs) seems to be a promising strategy for the treatment of neurodegenerative disorders, including Alzheimer's disease (AD). However, the clinical therapeutic effects of hAM-MSCs and their mechanisms of action in AD remain to be determined. Here, we used amyloid precursor protein (APP) and presenilin1 (PS1) double-transgenic mice to evaluate the effects of hAM-MSC transplantation on AD-related neuropathology and cognitive dysfunction. We found that hAM-MSC transplantation into the hippocampus dramatically reduced amyloid-β peptide (Aβ) deposition and rescued spatial learning and memory deficits in APP/PS1 mice. Interestingly, these effects were associated with increasing in Aβ-degrading factors, elevations in activated microglia, and the modulation of neuroinflammation. Furthermore, enhanced hippocampal neurogenesis in the subgranular zone (SGZ) of the dentate gyrus (DG) and enhanced synaptic plasticity following hAM-MSC treatment could be another important factor in reversing the cognitive decline in APP/PS1 mice. Instead, the mechanism underlying the improved cognition apparently involves a robust increase in hippocampal synaptic density and neurogenesis that is mediated by brain-derived neurotrophic factor (BDNF). In conclusion, our data suggest that hAM-MSCs may be a new and effective therapy for the treatment of AD.

Nuclear transcription factor Mesenchyme Homeobox 2 (MEOX2) is a homeobox gene that is originally discovered to suppress the growth of vascular smooth muscle and endothelial cells. However, whether or not it is connected to cancer is yet unknown. Here, we report that MEOX2 functions as a tumor-initiating element in glioma. Bioinformatic analyses of public databases and investigation of MEOX2 expression in patients with glioma demonstrated that MEOX2 was abundant at both mRNA and protein levels in glioma. MEOX2 expression was shown to be inversely linked with the prognosis of glioma patients. MEOX2 inhibition changed the morphology of glioma cells, inhibited cell proliferation and motility, whereas had no effect on cell apoptosis. Besides, silencing MEOX2 also hampered the epithelial-mesenchymal transition (EMT), focal adhesion formation, and F-actin assembly. Overexpression of MEOX2 exhibited opposite effects. Importantly, RNA-sequencing, ChIP-qPCR assay, and luciferase reporter assay revealed Cathepsin S (CTSS) as a novel transcriptional target of MEOX2 in glioma cells. Consistently, MEOX2 causes glioma tumor development in mice and greatly lowers the survival period of tumor-bearing mice. Our findings indicate that MEOX2 promotes tumorigenesis and progression of glioma partially through the regulation of CTSS. Targeting MEOX2-CTSS axis might be a promising alternative for the treatment of glioma.

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We previously reported that intraspinal transplantation of human amniotic mesenchymal stem cells (hAMSCs) promotes functional recovery in a rat model of acute traumatic spinal cord injury (SCI). However, whether intravenous transplantation of hAMSCs also has therapeutic benefit remains uncertain. In this study, we assessed whether intravenous transplantation of hAMSCs improves outcomes in rats with acute traumatic SCI. In addition, the potential mechanisms underlying the possible benefits of this therapy were investigated. Adult female Sprague–Dawley rats were subjected to SCI using a weight drop device, and then hAMSCs or PBS were administered after 2 h via the tail vein. Our results indicated that transplanted hAMSCs could migrate to injured spinal cord lesion. Compared with the control group, hAMSCs transplantation significantly decreased the numbers of ED1+ macrophages/microglia and caspase-3+ cells, and reduced levels of inflammatory cytokines, such as tumor necrosis factor alpha, interleukin-6 and IL-1β. In addition, hAMSCs transplantation significantly attenuated Evans blue extravasation, promoted angiogenesis and axonal regeneration. hAMSCs transplantation also significantly improved functional recovery. These results suggest that intravenous administration of hAMSCs provides neuroprotective effects in rats after acute SCI, and could be an alternative therapeutic approach for the treatment of acute SCI.