Overexpression of TG2 enhances the differentiation of ectomesenchymal stem cells into neuron ‑like cells and promotes functional recovery in adult rats following spinal cord injury.

Overexpression of TG2 enhances the differentiation of ectomesenchymal stem cells into neuron‑like cells and promotes functional recovery in adult rats following spinal cord injury. Mol Med Rep. 2019 Jul 15;: Authors: Shi W, Que Y, Lv D, Bi S, Xu Z, Wang D, Zhang Z Abstract Ectomesenchymal stem cells (EMSCs) represent a type of adult stem cells derived from the cranial neural crest. These cells are capable of self‑renewal and have the potential for multidirectional differentiation. Tissue transglutaminase type 2 (TG2) is a ubiquitously expressed member of the transglutaminase family of Ca2+‑dependent crosslinking enzymes. However, the effect of TG2 on neural differentiation and proliferation of EMSCs remains unknown. To determine whether TG2 improves EMSC proliferation and neurogenesis, a stable TG2‑overexpressing EMSC cell line (TG2‑EMSCs) was established by using an adenovirus system. Immunofluorescence staining and western blot analyses demonstrated that TG2 overexpression had beneficial effects on the rate of EMSC neurogenesis, and that the proliferative capacity of TG2‑EMSCs was higher than that of controls. Furthermore, the results of western blotting revealed that extracellular matrix (ECM) and neurotrophic factors were upregulated during the differentiation of TG2‑EMSCs. Notably, TG2‑EMSC transplantation in an animal model of spinal cord injury (SCI), TG2‑EMSCs differentiated into neuron‑like cells and enhanced the repair of SCI...
Source: Molecular Medicine Reports - Category: Molecular Biology Tags: Mol Med Rep Source Type: research

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Abstract Acute spinal cord injuries (ASCI) are common neural disorders in traumatology medicine. MicroRNA-210 (miR-210) plays a crucial role in cell survival, endothelial cell migration and cell regeneration. This paper is aim to validate the pathophysiological function of miR-210 on ASCI. We built a rat model of ASCI and utilized an adeno-associated virus (rAAV)-expressing miR-210 for stable over-expression of miR-210. We tested in vivo miR-210 gain of function on ASCI by microinjected rAAV-miR-210 into the rat spinal cord. We further screened the targeting genes of miR-210 by PCR array and detected relate...
Source: Tissue and Cell - Category: Cytology Authors: Tags: Tissue Cell Source Type: research
In this study, we investigated whether octamer transcription factor 1 (OCT1), a transcription factor, contributed to neuropathic pain caused by chronic constriction injury (CCI) of the sciatic nerve. Chronic constriction injury produced a time-dependent increase in the level of OCT1 protein in the ipsilateral L4/5 DRG, but not in the spinal cord. Blocking this increase through microinjection of OCT1 siRNA into the ipsilateral L4/5 DRG attenuated the initiation and maintenance of CCI-induced mechanical allodynia, heat hyperalgesia, and cold allodynia and improved morphine analgesia after CCI, without affecting basal respons...
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research
ConclusionAdv ‐HIF‐1α improves functional recovery in rats with SCI, and the underlying mechanism may be related to the mobilization of BMSCs to the injured area and higher expression levels of NT‐3 and BDNF.
Source: The Journal of Gene Medicine - Category: Genetics & Stem Cells Authors: Tags: RESEARCH ARTICLE Source Type: research
Retrogradely-transported neurotrophin signaling plays an important role in regulating neural circuit specificity. Here we investigated whether targeted delivery of neurotrophin-3 (NT-3) to lumbar motoneurons (MNs) caudal to a thoracic (T10) contusive spinal cord injury (SCI) could modulate dendritic patterning and synapse formation of the lumbar MNs.In vitro, Adeno-associated virus serotype 2 overexpressing NT-3 (AAV-NT-3) induced NT-3 expression and neurite outgrowth in cultured spinal cord neurons.In vivo, targeted delivery of AAV-NT-3 into transiently demyelinated adult mouse sciatic nerves led to the retrograde transpo...
Source: eLife - Category: Biomedical Science Tags: Neuroscience Source Type: research
In this study, we investigated the effects of the progression of SCI and potential regulation of apoptosis after the Pleckstrin homology (PH) domain and leucine rich repeat protein phosphatase 1 (PHLPP1) gene was silenced.Main methodsSpinal cord injection, and neuronal transfection with a recombinant adenovirus vector encoding small interfering RNA (siRNA) against PHLPP1 (AdsiPHLPP1) successfully silenced PHLPP1. These created in vivo and in vitro PHLPP1-silenced models, respectively, resulting in stable expression of the transgene in neurons.Key findingsThe results showed that silencing of PHLPP1 evidently reduced levels ...
Source: Life Sciences - Category: Biology Source Type: research
Conclusions: The current findings indicate that MST1 participates in SAH-induced BBB disruption and white matter fiber damage via the downstream NF-κB-MMP-9 signaling pathway. Therefore, MST1 antagonists may serve as a novel therapeutic target to prevent early brain injury in SAH patients. PMID: 30018671 [PubMed - in process]
Source: Behavioural Neurology - Category: Neurology Authors: Tags: Behav Neurol Source Type: research
by Michael D. Ehlers, MD, PhD Dr. Ehlers is with Biogen in Cambridge, Massachusetts. Innov Clin Neurosci. 2018;15(3–4):15–16 Funding: No funding was received for the preparation of this article. Disclosures: Dr. Ehlers is an employee and shareholder at Biogen Inc. in Cambridge, Massachusetts. Prominent and expensive failures in Alzheimer’s disease therapies have led to a contagious belief system in some parts of the biopharma industry that neuroscience is just too hard, too risky, and too uncertain. But, might this belief system itself be a residual bias of the past? Close inspection reveals all the signs...
Source: Innovations in Clinical Neuroscience - Category: Neuroscience Authors: Tags: Commentary Current Issue Source Type: research
In this study, the Ad-GFP-HO-1C[INCREMENT]23 group showed better kinematic functional recovery after SCI than the Ad-GFP and Vehicle groups, as well as smaller reductions in TJ proteins and capillary permeability compared with those in the Ad-GFP and Vehicle groups. These findings indicated that Ad-GFP-HO-1C[INCREMENT]23 might have a potential therapeutic effect that is mediated by its protection of BSCB integrity.
Source: NeuroReport - Category: Neurology Tags: Clinical Neuroscience Source Type: research
Abstract Damage to respiratory neural circuitry and consequent loss of diaphragm function is a major cause of morbidity and mortality in individuals suffering from traumatic cervical spinal cord injury (SCI). Repair of CNS axons after SCI remains a therapeutic challenge, despite current efforts. SCI disrupts inspiratory signals originating in the rostral ventral respiratory group (rVRG) of the medulla from their phrenic motor neuron (PhMN) targets, resulting in loss of diaphragm function. Using a rat model of cervical hemisection SCI, we aimed to restore rVRG-PhMN-diaphragm circuitry by stimulating regeneration of...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research
CONCLUSION: Taking all these data together, it is suggested that the increased neuroglobin expression could improve the locomotor function. PMID: 29141514 [PubMed - as supplied by publisher]
Source: Journal of Spinal Cord Medicine - Category: Orthopaedics Tags: J Spinal Cord Med Source Type: research
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