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Bone Marrow Mesenchymal Stem Cell-Derived Exosomal KLF4 Alleviated Ischemic Stroke Through Inhibiting N6-Methyladenosine Modification Level of Drp1 by Targeting lncRNA-ZFAS1
AbstractIschemic stroke has  become a serious public health problem that causes high rates of death and disability. Bone marrow mesenchymal stem cell (BMSC)-derived exosomes have shown promising therapeutic results in IS, while the underlying mechanisms need further investigation. Cell and mice models were established through oxygen–glucose deprivation/reoxygenation (OGD/R) treatment and middle cerebral artery occlusion (MCAO)/reperfusion. Exosomes were isolated from BMSCs. Related gene and protein expression was measured by qRT-PCR, Western blotting, and immunofluorescence analysis. The biological functions of treate d...
Source: Molecular Neurobiology - May 28, 2023 Category: Neurology Source Type: research

From Hair to the Brain: The Short-Term Therapeutic Potential of Human Hair Follicle-Derived Stem Cells and Their Conditioned Medium in a Rat Model of Stroke
We describe here for the first time the therapeutic potential of human hair follicle-derived stem cells (hHFSCs) and their conditioned medium (CM) in a rat model of IS. Furthermore, we hypothesized that a combination of cell therapy with repeated CM administration might enhance the restorative efficiency of this approach compared to each treatment alone. Middle cerebral artery occlusion was performed for 30  min to induce IS. Immediately after reperfusion, hHFSCs were transplanted through the intra-arterial route and/or hHFSC-CM administered intranasally. The neurological outcomes, short-term spatial working memory, and i...
Source: Molecular Neurobiology - March 25, 2023 Category: Neurology Source Type: research

Paracrine Effects of Mesenchymal Stem Cells in Ischemic Stroke: Opportunities and Challenges
AbstractIt is well acknowledged that neuroprotective effects of transplanted mesenchymal stem cells (MSCs) in ischemic stroke are attributed to their paracrine-mediated actions or bystander effects rather than to cell replacement in infarcted areas. This therapeutic plasticity is due to MSCs ’ ability to secrete a broad range of bioactive molecules including growth factors, trophic factors, cytokines, chemokines, and extracellular vesicles, overall known as the secretome. The secretome derivatives, such as conditioned medium (CM) or purified extracellular vesicles (EVs), exert remarka ble advantages over MSC transplantat...
Source: Molecular Neurobiology - August 3, 2022 Category: Neurology Source Type: research

Post-stroke Impairment of the Blood –Brain Barrier and Perifocal Vasogenic Edema Is Alleviated by Endovascular Mesenchymal Stem Cell Administration: Modulation of the PKCδ/MMP9/AQP4-Mediated Pathway
AbstractPost-stroke edema and upregulation of aquaporin 4 (AQP4) water transport channels play a significant role in the progression of stroke pathology and deteriorating stroke outcomes. Prior studies from our lab have demonstrated the safety and efficacy of intra-arterial (IA) 1  × 105 mesenchymal stem cells (MSCs) administration post-stroke towards functional restoration and neuroprotection. Protein kinases have been reported to be involved in the signaling cascade of edema, with evidence supporting both its upregulation and downregulation at 24  h post-stroke. Among different protein kinase C (PKC) isoforms, the ...
Source: Molecular Neurobiology - February 21, 2022 Category: Neurology Source Type: research

Insights of Extracellular Vesicles of Mesenchymal Stem Cells: a Prospective Cell-Free Regenerative Medicine for Neurodegenerative Disorders
AbstractMesenchymal stem cells (MSCs) are multipotent, adult stem cells which are found in numerous tissues like the umbilical cord, Wharton ’s jelly, bone marrow, and adipose tissue. They possess the capacity of self-renewal by dividing and differentiating into various cellular lineages. Their characteristic therapeutic potential exploited so far has made them a desirable candidate in regenerative medicine. Neurodegenerative diseases (NDs) like Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), and ischemic stroke have been treated with MSCs and MSC-...
Source: Molecular Neurobiology - October 29, 2021 Category: Neurology Source Type: research

Proteomics-Guided Study on Buyang Huanwu Decoction for Its Neuroprotective and Neurogenic Mechanisms for Transient Ischemic Stroke: Involvements of EGFR/PI3K/Akt/Bad/14-3-3 and Jak2/Stat3/Cyclin D1 Signaling Cascades
AbstractBuyang Huanwu Decoction (BHD), a classic traditional Chinese medicine (TCM) formula, has been used for recovering neurological dysfunctions and treating post-stroke disability in China for 200  years. In the present study, we investigated the effects of BHD on inhibiting neuronal apoptosis, promoting proliferation and differentiation of neural stem cells (NSCs) and neurite formation and enhancing learning and memory functional recovery in an experimental rat ischemic stroke model. BHD si gnificantly reduced infarct volume and decreased cell apoptosis in the ischemic brain. BHD enhanced neuronal cell viability in v...
Source: Molecular Neurobiology - September 2, 2020 Category: Neurology Source Type: research

Glia-Like Cells from Late-Passage Human MSCs Protect Against Ischemic Stroke Through IGFBP-4
AbstractStem cell therapy is considered to be a promising future treatment for intractable neurological diseases, although all the clinical trials using stem cells have not yet shown any good results. Early passage mesenchymal stem cells (MSCs) have been used in most clinical trials because of the issues on safety and efficacy. However, it is not easy to get plenty of cells enough for the treatment and it costs too much. Lots of late passage MSCs can be obtained at lower cost but their efficacy would be a big hurdle for clinical trials. If late passage MSCs with better efficacy could be used in clinical trials, it could be...
Source: Molecular Neurobiology - October 26, 2019 Category: Neurology Source Type: research

Chondroitin Sulfate Impairs Neural Stem Cell Migration Through ROCK Activation
AbstractBrain injuries such as trauma and stroke lead to glial scar formation by reactive astrocytes which produce and secret axonal outgrowth inhibitors. Chondroitin sulfate proteoglycans (CSPG) constitute a well-known class of extracellular matrix molecules produced at the glial scar and cause growth cone collapse. The CSPG glycosaminoglycan side chains composed of chondroitin sulfate (CS) are responsible for its inhibitory activity on neurite outgrowth and are dependent on RhoA activation. Here, we hypothesize that CSPG also impairs neural stem cell migration inhibiting their penetration into an injury site. We show tha...
Source: Molecular Neurobiology - May 5, 2017 Category: Neurology Source Type: research

Direct Conversion of Somatic Cells into Induced Neurons
AbstractThe progressive loss and degeneration of neurons in the central nervous system (CNS), as a result of traumas or diseases including Alzheimer ’s, Parkinson’s, Huntington’s disease, stroke, and traumatic injury to the brain and spinal cord, can usually have devastating effects on quality of life. The current strategies available for treatments are described including drug delivery, surgery, electrical stimulation, and cell-based tiss ue engineering approaches. However, apart from cell-based therapy, other attempts are limited in improving clinical outcomes. Recently, stem cell and neural stem cell (NSC) in part...
Source: Molecular Neurobiology - December 15, 2016 Category: Neurology Source Type: research

Exogenous Neural Stem Cells Transplantation as a Potential Therapy for Photothrombotic Ischemia Stroke in Kunming Mice Model
In this study, we explore the transplantation of exogenous neural stem cells (NSCs) as the potential therapy for the photothrombotic ischemia stroke in a Kunming mice model. After stroke, mice receiving NSC transplantation demonstrated a better recovery of brain function during the neurobehavioral tests. Histology analysis of the brain samples from NSC transplanted mice demonstrated a reduction of brain damage caused by stroke. Moreover, immunofluorescence assay for biomarkers in brain sections confirmed that transplanted NSCs indeed differentiated to neurons and astrocytes, consistent with the improved brain function afte...
Source: Molecular Neurobiology - January 28, 2016 Category: Neurology Source Type: research

Neuroprotective Effects of Acetyl-L-Carnitine Against Oxygen-Glucose Deprivation-Induced Neural Stem Cell Death
Abstract Deprivation of oxygen and glucose is the main cause of neuronal cell death during cerebral infarction and can result in severe morbidity and mortality. In general, the neuroprotective therapies that are applied after ischemic stroke have been unsuccessful, despite many investigations. Acetyl-L-carnitine (ALCAR) plays an important role in mitochondrial metabolism and in modulating the coenzyme A (CoA)/acyl-CoA ratio. We investigated the protective effects of ALCAR against oxygen-glucose deprivation (OGD) in neural stem cells (NSCs). We measured cell viability, proliferation, apoptosis, and intracellular si...
Source: Molecular Neurobiology - December 8, 2015 Category: Neurology Source Type: research

Bone Marrow-Derived Endothelial Progenitor Cells Protect Against Scopolamine-Induced Alzheimer-Like Pathological Aberrations
Abstract Vascular endothelial dysfunction plays a key role in the pathogenesis of Alzheimer’s disease (AD). Patients with AD have displayed decreased circulating endothelial progenitor cells (EPCs) which repair and maintain the endothelial function. Transplantation of EPCs has emerged as a promising approach for the management of cerebrovascular diseases including ischemic stroke, however, its impact on AD has been poorly described. Thus, the current study aimed at investigating the effects of bone marrow-derived (BM) EPCs transplantation in repeated scopolamine-induced cognitive impairment, an experimental mode...
Source: Molecular Neurobiology - December 20, 2014 Category: Neurology Source Type: research

Hypoxia/Reoxygenation-Preconditioned Human Bone Marrow-Derived Mesenchymal Stromal Cells Rescue Ischemic Rat Cortical Neurons by Enhancing Trophic Factor Release
In this study, we assessed whether hypoxia/reoxygenation (H/R) preconditioning of human BM-MSCs could increase their functional capacity and beneficial effect on ischemic rat cortical neurons. Human BM-MSCs were cultured under hypoxia (1 % O2) and with long-term reoxygenation for various times to identify the optimal conditions for increasing their viability and proliferation. The effects of H/R preconditioning on the BM-MSCs were assessed by analyzing the expression of prosurvival genes, trophic factors, and cell migration assays. The functionally improved BM-MSCs were cocultured with ischemic rat cortical neurons to com...
Source: Molecular Neurobiology - October 7, 2014 Category: Neurology Source Type: research