Glial Stem Research Articles

Segmentation and classification of specific pattern of Brain tumor using CNN

A Brain tumor is a growth of cells in the brain or near it. Brain tumors can happen in the brain tissue close by locations include nerves, the pituitary gland, central nervous system , meninges and the membranes that cover the surface of the brain[1]. A glioma is a tumor that forms in the brain or spinal cord A glioma is a tumor of the central nervous system that makes an appearance from glial stem or progenitor cells. Glial cells are a type of cell generally present in the nervous system. Gliomas predominantly occur in the brain and, rarely, in the spinal cord. They grow in approximately 6.6 per 100,000 individuals each year. They transpire at various ages, controlled by the subtype. Growing gliomas can compact areas of the brain where they occur and cause various symptoms including headaches, nausea, vomiting, cognitive impairment, seizures, gait imbalance, language impairment [2] A meningioma is a tumor that makes an appearance from the meninges — the membranes that surround the brain and spinal cord. In spite of the fact that not technically a brain tumor, it is included in this category because it may compress or squeeze the adjacent brain, nerves and vessels Meningiomas are tumors of the meninges, mostly benign and often managed by surgical resection, with radiation therapy and chemotherapy reserved for high-risk or refractory disease.[3]. Tumors can start nearly anywhere in the body. Tumors that start in the pituitary gland are called pituitary tumors. The anterior pituitary tumors start in the larger, front part of the pituitary gland known as the anterior pituitary. The posterior pituitary: The smaller, back part of the pituitary gland is an extension of brain tissue from the hypothalamus. The posterior pituitary stores and releases hormones made by the hypothalamus (vasopressin and oxytocin) into the bloodstream [4]. Machine learning applications in healthcare are already having a positive impact, and its potential is still in the early stages of being realized to deliver care[2]. In the future, machine learning in healthcare will become increasingly important as we strive to make sense of the ever-growing clinical data sets in healthcare. Heart disease cancer, and brain tumors are diagnosed using medical imaging procedures such as MRI scans, CT scans, and ECG. As a result, deep learning assists doctors in better analyzing diseases and providing the best treatment to patients. In this paper specific brain tumor segmentation and classification have been done using a Deep Convolutional Neural Network that incorporates a multiscale approach. . The proposed neural model can look over MRI images containing three types of tumors: glioma, meningioma, and pituitary tumor. Data has been collected from https://www.kaggle.com/datasets/masoudnickparvar/brain-tumor-mri-dataset?select=Training This dataset ecompasses 7023 images of human brain MRI images which are classified into 4 classes: glioma - meningioma - no tumor and pituitary. no tumor class images were taken from the Br35H dataset. The goal of this work was to aid clinical researchers in gaining a clear and intuitive understanding of the application of data-mining technology on clinical data to promote the production of research results that are beneficial to doctors and patients.

Differential expression of stem cell markers in proliferating cells in glioma

PurposeThe identification of prognostically and therapeutically relevant molecular markers is fundamental to the further development of personalised therapies in brain tumours. Current therapeutic options for the treatment of gliomas rely mainly on surgical resection and the inhibition of tumour cell proliferation by irradiation and chemotherapy. Glioma stem cells are a subpopulation of proliferating tumour cells that have self-renewal capacity and can give rise to heterogeneous cells that comprise the tumour and are thought to play a role in the resistance of gliomas to therapy. The aim of this study was to evaluate the expression of markers of glioma stem cells and differentiated glial cells in proliferating glioma cells in comparison to the overall expression of the respective markers in the tumour tissue.MethodsTissue microarrays were assembled from specimen of pilocytic astrocytoma, diffuse astrocytoma, anaplastic astrocytoma, glioblastoma, oligodendroglioma, anaplastic oligodendroglioma, ependymoma, and anaplastic ependymoma. These were immunohistochemically double stained with antibodies against the proliferation-associated antigen Ki67 and marker proteins for glioma stem cells (CD133, Nestin, Musashi, CD15, CD44), and differentiated glioma cells (GFAP, MAP2c).ResultsThe expression of both glial and glioma stem cell markers differs between proliferating and non-proliferating glioma cells. Furthermore, the proliferating cells in the different glial tumour entities show a different expression profile.ConclusionFurther analysis of marker expression in proliferating glioma cells and correlation with clinical outcome and susceptibility to irradiation and chemotherapy might help establish new biomarkers and therapies for glioma.

Intra-arterial transplantation of stem cells in large animals as a minimally-invasive strategy for the treatment of disseminated neurodegeneration

Stem cell transplantation proved promising in animal models of neurological diseases; however, in conditions with disseminated pathology such as ALS, delivery of cells and their broad distribution is challenging. To address this problem, we explored intra-arterial (IA) delivery route, of stem cells. The goal of this study was to investigate the feasibility and safety of MRI-guided transplantation of glial restricted precursors (GRPs) and mesenchymal stem cells (MSCs) in dogs suffering from ALS-like disease, degenerative myelopathy (DM). Canine GRP transplantation in dogs resulted in rather poor retention in the brain, so MSCs were used in subsequent experiments. To evaluate the safety of MSC intraarterial transplantation, naïve pigs (n = 3) were used as a pre-treatment control before transplantation in dogs. Cells were labeled with iron oxide nanoparticles. For IA transplantation a 1.2-French microcatheter was advanced into the middle cerebral artery under roadmap guidance. Then, the cells were transplanted under real-time MRI with the acquisition of dynamic T2*-weighted images. The procedure in pigs has proven to be safe and histopathology has demonstrated the successful and predictable placement of transplanted porcine MSCs. Transplantation of canine MSCs in DM dogs resulted in their accumulation in the brain. Interventional and follow-up MRI proved the procedure was feasible and safe. Analysis of gene expression after transplantation revealed a reduction of inflammatory factors, which may indicate a promising therapeutic strategy in the treatment of neurodegenerative diseases.

Proteolytic Rafts for Improving Intraparenchymal Migration of Minimally Invasively Administered Hydrogel-Embedded Stem Cells.

The physiological spaces (lateral ventricles, intrathecal space) or pathological cavities (stroke lesion, syringomyelia) may serve as an attractive gateway for minimally invasive deployment of stem cells. Embedding stem cells in injectable scaffolds is essential when transplanting into the body cavities as they secure favorable microenvironment and keep cells localized, thereby preventing sedimentation. However, the limited migration of transplanted cells from scaffold to the host tissue is still a major obstacle, which prevents this approach from wider implementation for the rapidly growing field of regenerative medicine. Hyaluronan, a naturally occurring polymer, is frequently used as a basis of injectable scaffolds. We hypothesized that supplementation of hyaluronan with activated proteolytic enzymes could be a viable approach for dissolving the connective tissue barrier on the interface between the scaffold and the host, such as pia mater or scar tissue, thus demarcating lesion cavity. In a proof-of-concept study, we have found that collagenase and trypsin immobilized in hyaluronan-based hydrogel retain 60% and 28% of their proteolytic activity compared to their non-immobilized forms, respectively. We have also shown that immobilized enzymes do not have a negative effect on the viability of stem cells (glial progenitors and mesenchymal stem cells) in vitro. In conclusion, proteolytic rafts composed of hyaluronan-based hydrogels and immobilized enzymes may be an attractive strategy to facilitate migration of stem cells from injectable scaffolds into the parenchyma of surrounding tissue.

Glial stem and progenitor cells shape the brain--in ontogeny, phylogeny, and disease. Foreword.

Glial stem and progenitor cells shape the brain--in ontogeny, phylogeny, and disease. Foreword.

CB-09 * THE CELL OF ORIGIN FOR GLIOBLASTOMA CONTRIBUTES TO THE PHENOTYPIC HETEROGENEITY OF GLIOMA STEM CELLS

Glioblastoma Multiforme (GBM) is the most frequent adult primary malignant brain tumor that remains incurable despite aggressive treatment. The cell of origin (COO) for GBM is unknown but assumed to be a glial stem or progenitor cell. GBM harbours hierarchical tumor cells called glioma stem cells (GSCs) that maintain tumor growth, drive tumor progression and cause tumor relapse due to their increased resistance to therapy. We have analyzed the significance of cellular origin for GBM development and GSC properties by comparing mouse GBMs and GSCs derived thereof induced in neural stem cells (NSCs), glial-restricted precursor cells (GPCs) or oligodendrocyte precursor cells (OPCs) by identical mutations. There were striking differences in GBM development and the phenotypes of GSCs and their response to drugs owing to the COO. Global gene expression analysis of mouse GSC lines displayed a clear separation due to COO and differential gene expression analysis identified a COO gene signature of 175 genes. Cross-species bioinformatics analyses were performed. First we analyzed the human cancer genome atlas (TCGA) GBM tissue samples and the mouse GSC expression data for a collection of TCGA GBM subtype signature genes. This showed that we could model both Proneural and Mesenchymal GBMs in mice by merely switching the COO. Next, we used the mouse COO gene signature to stratify a large number of newly established human glioma stem cell lines. This produced two groups of human GSCs; the NSC origin group and the progenitor cell (PC) origin group in which the mouse GPC- and OPC-derived genes were combined. Importantly, patient survival was significantly different between the NSC and PC COO groups with a better prognosis for the PC group patients. Thus, the cell of origin is essential for GBM biology and needs to be considered for more accurate patient stratification, target identification and drug discovery.

Paying attention to optic nerve injury disease and optic nerve regeneration study

Glaucoma,optical neuritis and trauma are optic nerve injury-related diseases.These ocular diseases cause irreversible damage of the vision and even blindness.The study on optic nerve regeneration is a powerful approach for rescuing vision and improving the quality of life of patients.Therefore,how to promote optic nerve regeneration is always the focus in ophthalmology.In recent years,great progression has achieved by modulation of cellular signal pathway,usage of glial cells,stem cells and neurotrophic factor,etc,which lays a basis for the treatment of optic nerve injury.Ophthalmologist should trace and participate in these researches to promote the development of regeneration medicine.This review summarizes these new approaches after discussing factors effecting optic nerve regeneration briefly and proposes questions to answer. Key words: Optic nerve/regeneration; Retinal ganglion cell; Glia cell; Stem cell; Neurotrophic factor

Abstract 3480: XIAP inhibitors prime glioblastoma cells for γ-irradiation-induced apoptosis and circumvent radioresistance of glioblastoma stem cells

Abstract Resistance to radiotherapy remains a major challenge in the treatment of glioblastoma and may be caused by evasion of apoptosis. Since antiapoptotic proteins such as XIAP block apoptosis at the effector phase, XIAP presents a promising target to break radioresistance. In the present study, we therefore investigated the effect of small molecule XIAP inhibitors on radiosensitivity of glioblastoma and corresponding normal cells using glioblastoma cell lines, primary glioblastoma explant cultures, glioblastoma stem cells as well as neurons, glial and neural stem cells. Here, we report that XIAP inhibitors overcome radioresistance of glioblastoma and even target the glioblastoma cancer stem cell population without increasing radiosensitivity of non-malignant cells. XIAP inhibitors significantly enhance γ-irradiation-induced apoptosis in a panel of glioblastoma cell lines. Also, XIAP inhibitors cooperate with γ-irradiation to suppress clonogenic growth of glioblastoma cells demonstrating that the combination treatment affects long-term survival. Analysis of signaling pathways reveals that XIAP inhibitors significantly increase γ-irradiation-triggered loss of mitochondrial membrane potential, cytochrome c release and activation of caspases. Interestingly, inhibition of caspases reduces the cooperative effect of XIAP inhibitors and γ-irradiation to cause mitochondrial perturbations suggesting that XIAP inhibitors initiate a feedback amplification loop back to mitochondria by enhancing caspase activity. By comparison, XIAP inhibition does no alter DNA damage/DNA repair, activation of NF-κB or cell cycle arrest following γ-irradiation indicating that XIAP inhibition has no impact on the initial damage and/or cellular stress response. Of note, XIAP inhibitors also prime patients’ derived, primary glioblastoma cells for γ-irradiation-triggered apoptosis. Since glioblastoma stem cells have recently been implicated in radioresistance of glioblastoma, we also tested the effect of XIAP inhibitors on the cancer stem cell population. Intriguingly, XIAP inhibitors restore sensitivity to γ-irradiation in glioblastoma stem cells that were isolated from fresh glioblastoma surgical specimens. In contrast to malignant cells, XIAP inhibitors alone or in combination with γ-irradiation exert no cytotoxicity on non-transformed cells of the central nervous system including neurons, glial and neural stem cells, pointing to a therapeutic window. Thus, small molecule XIAP inhibitors present a promising new strategy to overcome radioresistance of glioblastoma including glioblastoma stem cells. These findings have important implications for further (pre)clinical evaluation of XIAP inhibitors for radiosensitization of glioblastoma. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3480.

Expression of Inhibin α, Glial Cell Line-Derived Neurotrophic Factor and Stem Cell Factor in Sertoli Cell-Only Syndrome: Relation to Successful Sperm Retrieval by Microdissection Testicular Sperm Extraction

Expression of Inhibin α, Glial Cell Line-Derived Neurotrophic Factor and Stem Cell Factor in Sertoli Cell-Only Syndrome: Relation to Successful Sperm Retrieval by Microdissection Testicular Sperm Extraction

A role for ion channels in glioma cell invasion.

Many cells, including neuronal and glial progenitor cells, stem cells and microglial cells, have the capacity to move through the extracellular spaces of the developing and mature brain. This is particularly pronounced in astrocyte-derived tumors, gliomas, which diffusely infiltrate the normal brain. Although a significant body of literature exists regarding signals that are involved in the guidance of cells and their processes, little attention has been paid to cell-shape and cell-volume changes of migratory cells. However, extracellular spaces in the brain are very narrow and represent a major obstacle that requires cells to dynamically regulate their volume. Recent studies in glioma cells show that this involves the secretion of Cl(-) and K(+) with water. Pharmacological inhibition of Cl(-) channels impairs their ability to migrate and limits tumor progression in experimental tumor models. One Cl(-)-channel inhibitor, chlorotoxin, is currently in Phase II clinical trials to treat malignant glioma. This article reviews our current knowledge of cell-volume changes and the role of ion channels during the migration of glioma cells. It also discusses evidence that supports the importance of channel-mediated cell-volume changes in the migration of immature neurons and progenitor cells during development. New unpublished data is presented, which demonstrates that Cl(-) and K(+) channels involved in cell shrinkage localize to lipid-raft domains on the invadipodia of glioma cells and that their presence might be regulated by trafficking of these proteins in and out of lipid rafts.

The ultrastructure of preretinal macular fibrosis

A case of preretinal macular fibrosis, following long-standing central vein occlusion and hemorrhagic glaucoma, was examined macroscopically and electron-microscopically. Pretreatment with cyclodiathermy puncture was performed twice before enucleation. The following morphologic results were observed: 1. Epiretinal cell layers in the peripapillar and foveolar regions which caused no 'puckering' of the retinal surface. These cell layers were mainly composed of glial cells. Some Müller cell processes and macrophages were also present. The epiretinal glial cells stem from the surface of the papilla and of the retina. They leave the retina through breaks of the basal lamina (especially where the latter is only a thin layer). 2. Folding (puckering) of the retinal surface was exclusively observed under condensed masses of fibrous tissue. The epiretinal fibrous tissue is composed of immature collagen fibrils of various diameters, of acid glycosaminoglycans, and of granular deposits of long-spacing collagen. The fibrillar material is firmly attached to the basal lamina of the retina. Shrinkage of the epiretinal fibrous tissue similar to the shrinkage of scar tissue is assumed to be the reason for the development of traction to the retinal surface. The epiretinal glial cells are assumed to be the sites of synthesis of the preretinal fibrous masses and glycosaminoglycans.