scholarly journals Adult Neural Stem Cells: Basic Research and Production Strategies for Neurorestorative Therapy

2018 ◽  
Vol 2018 ◽  
pp. 1-18 ◽  
Author(s):  
E. M. Samoilova ◽  
V. A. Kalsin ◽  
N. M. Kushnir ◽  
D. A. Chistyakov ◽  
A. V. Troitskiy ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Nervous Tissue ◽  
Molecular Mechanisms ◽  
Somatic Cells ◽  
Basic Research ◽  
Neural Cells ◽  
Pluripotent State ◽  
Increased Risk ◽  
Object Of Study

Over many decades, constructing genetically and phenotypically stable lines of neural stem cells (NSC) for clinical purposes with the aim of restoring irreversibly lost functions of nervous tissue has been one of the major goals for multiple research groups. The unique ability of stem cells to maintain their own pluripotent state even in the adult body has made them into the choice object of study. With the development of the technology for induced pluripotent stem cells (iPSCs) and direct transdifferentiation of somatic cells into the desired cell type, the initial research approaches based on the use of allogeneic NSCs from embryonic or fetal nervous tissue are gradually becoming a thing of the past. This review deals with basic molecular mechanisms for maintaining the pluripotent state of embryonic/induced stem and reprogrammed somatic cells, as well as with currently existing reprogramming strategies. The focus is on performing direct reprogramming while bypassing the stage of iPSCs which is known for genetic instability and an increased risk of tumorigenesis. A detailed description of various protocols for obtaining reprogrammed neural cells used in the therapy of the nervous system pathology is also provided.

P14.59 Rapid early progression of glioblastoma is not related to cortical/neural stem cells regions

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii49-ii49
Author(s):  
T Kazda ◽  
R Lakomy ◽  
I Selingerova ◽  
P Pospisil ◽  
L Hynkova ◽  
...  
Keyword(s):  
Stem Cells ◽  
Overall Survival ◽  
Neural Stem Cells ◽  
Spatial Relationship ◽  
Clinical Biomarkers ◽  
Increased Risk ◽  
Initial Location ◽  
Early Progression ◽  
Multifocal Tumor ◽  
Relationship Of

Abstract BACKGROUND Rapid early progression (REP) of glioblastoma after surgery observed on pre-radiotherapy MRI scan is common. Subventricular zone (SVZ) and hippocampal regions are supposed to harbor astrocyte-like neural stem cells (NSC) with tumors arising from these transformed stem cells threatening of higher risk of REP. REP is defined as a new enhancing tumor or >25% increase in enhancement before radiotherapy. Lim′s classification of initial glioblastoma location related to these NSC regions predicts invasive and multifocal tumor phenotype. Glioblastomas are classified preoperatively into four groups by the spatial relationship of the contrast-enhancing lesion with the SVZ and cortex. The aim of this retrospective single-institutional study is to evaluate the relations of this Lim classification on REP in unselected cohort of glioblastoma patients. MATERIAL AND METHODS Patients receiving radiotherapy between 2014–2017 were analyzed, 95 were evaluable. 47 patients (30.5%) were treated with the Stupp regimen. Lim1 classification (contact with cortex as well as SVZ) was presented in 74(48%) patients, Lim2 (contact with SVZ only) in 22(14.3%), Lim3 (contact with cortex only) in 50(32.5%) and Lim4 in 8(5.2%) patients. A total of 52% of patients developed REP. RESULTS Significantly better overall survival was with Stupp regimen (23.3 vs. 8.6 months, p<0.001) and without REP (18.5 vs. 10.2 months, p=0.001). There was no significant impact of time to start of radiotherapy. No significant relation between REP and Lim classification was observed. CONCLUSION The initial location is not predictive for REP. Patients experiencing REP have significantly worse overall survival and modification of their management represents an urgent unmet clinical need. Molecular and clinical biomarkers indicating an increased risk of REP are needed.Presented will also be an already published analysis of clinical factors associated with REP in glioblastoma and the effect of REP and treatment on survival outcomes. Newly, we will introduce the investigator-initiated prospective academic clinical trial (GlioMET) focused on optimization of glioblastoma radiotherapy by 11C-Methionine PET scan in patients with REP. Supported by Ministry of Health of the Czech Republic AZV, No.18-03-00469 and AZV NU20-03-00148.

scholarly journals Loss of postnatal quiescence of neural stem cells through mTOR activation upon genetic removal of cysteine string protein-α

2019 ◽  
Vol 116 (16) ◽  
pp. 8000-8009 ◽  
Author(s):  
Jose L. Nieto-González ◽  
Leonardo Gómez-Sánchez ◽  
Fabiola Mavillard ◽  
Pedro Linares-Clemente ◽  
María C. Rivero ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Neural Stem Cell ◽  
Molecular Mechanisms ◽  
Radial Glia ◽  
Brain Dysfunction ◽  
Mtor Signaling ◽  
Cysteine String Protein ◽  
Newborn Neurons

Neural stem cells continuously generate newborn neurons that integrate into and modify neural circuitry in the adult hippocampus. The molecular mechanisms that regulate or perturb neural stem cell proliferation and differentiation, however, remain poorly understood. Here, we have found that mouse hippocampal radial glia-like (RGL) neural stem cells express the synaptic cochaperone cysteine string protein-α (CSP-α). Remarkably, in CSP-α knockout mice, RGL stem cells lose quiescence postnatally and enter into a high-proliferation regime that increases the production of neural intermediate progenitor cells, thereby exhausting the hippocampal neural stem cell pool. In cell culture, stem cells in hippocampal neurospheres display alterations in proliferation for which hyperactivation of the mechanistic target of rapamycin (mTOR) signaling pathway is the primary cause of neurogenesis deregulation in the absence of CSP-α. In addition, RGL cells lose quiescence upon specific conditional targeting of CSP-α in adult neural stem cells. Our findings demonstrate an unanticipated cell-autonomic and circuit-independent disruption of postnatal neurogenesis in the absence of CSP-α and highlight a direct or indirect CSP-α/mTOR signaling interaction that may underlie molecular mechanisms of brain dysfunction and neurodegeneration.

Die Kunst des Neuronenschmiedens: Direkte Reprogrammierung somatischer Zellen in induzierte neuronale Zellen

e-Neuroforum ◽  
2013 ◽  
Vol 19 (2) ◽  
Author(s):  
Marisa Karow ◽  
Benedikt Berninger
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Neuronal Cells ◽  
Somatic Cells ◽  
Cell Types ◽  
Direct Conversion ◽  
Cellular Reprogramming ◽  
Direct Reprogramming ◽  
Brain Pericytes

AbstractThe art of forging neurons: direct reprogramming of somatic cells into induced neu­ronal cells.Cellular reprogramming has shed new light on the plasticity of terminally differentiated cells and discloses novel strategies for cell-based therapies for neurological disorders. With accumulating knowledge of the programs underlying the genesis of the distinct neural cell types, especially with the identification of relevant transcription factors and microRNAs, reprogramming of somatic cells of different origins into induced neuronal cells or neural stem cells has been successfully achieved. Starting with the general con­cept of reprogramming we discuss here three different paradigms: 1) direct conversion of CNS-foreign cells such as skin fibroblasts into induced neuronal cells or neural stem cells; 2) transdifferentiation of CNS resident cells such as astrocytes and brain pericytes into induced neuronal cells; 3) reprogramming of one neuronal subtype into another. The latter has already been successfully achieved in vivo during early brain develop­ment, providing strong impulse for the attempt to succeed in direct reprogramming in situ for future brain repair.

Brain tumor stem cells

2010 ◽  
Vol 391 (6) ◽  
Author(s):  
Thomas Palm ◽  
Jens C. Schwamborn
Keyword(s):  
Stem Cells ◽  
Brain Tumor ◽  
Neural Stem Cells ◽  
Molecular Mechanisms ◽  
Adult Brain ◽  
Tumor Stem Cells ◽  
Cellular Mechanisms ◽  
Cell Pool ◽  
Brain Tumor Stem Cells ◽  
Stem Cell Pool

Abstract Since the end of the ‘no-new-neuron’ theory, emerging evidence from multiple studies has supported the existence of stem cells in neurogenic areas of the adult brain. Along with this discovery, neural stem cells became candidate cells being at the origin of brain tumors. In fact, it has been demonstrated that molecular mechanisms controlling self-renewal and differentiation are shared between brain tumor stem cells and neural stem cells and that corruption of genes implicated in these pathways can direct tumor growth. In this regard, future anticancer approaches could be inspired by uncovering such redundancies and setting up treatments leading to exhaustion of the cancer stem cell pool. However, deleterious effects on (normal) neural stem cells should be minimized. Such therapeutic models underline the importance to study the cellular mechanisms implicated in fate decisions of neural stem cells and the oncogenic derivation of adult brain cells. In this review, we discuss the putative origins of brain tumor stem cells and their possible implications on future therapies.

scholarly journals Comparison of effects of a selective 5-HT reuptake inhibitor versus a 5-HT4 receptor agonist on in vivo neurogenesis at the rectal anastomosis in rats

2012 ◽  
Vol 302 (6) ◽  
pp. G588-G597 ◽  
Author(s):  
Isao Kawahara ◽  
Hiroki Kuniyasu ◽  
Hiroko Matsuyoshi ◽  
Kei Goto ◽  
Koji Obata ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Nerve Fiber ◽  
Reuptake Inhibitor ◽  
Guinea Pigs ◽  
Neural Circuit ◽  
Neural Cells ◽  
Anastomotic Site ◽  
Fiber Tract

It was recently reported that activation of enteric neural 5-HT4 receptors (SR4) promotes reconstruction of enteric neural circuit injury in distal gut of guinea pigs and that this reconstruction involves neural stem cells. We aimed to explore a novel approach using a selective serotonin reuptake inhibitor (SSRI), which increases endogenous 5-HT, to repair enteric nerve fiber injury in the rat distal gut. Enteric nerve fiber injury was performed by rectal transection and subsequent end-to-end one-layer anastomosis. The SSRI fluvoxamine maleate (100 μmol/l) was applied locally at the anastomotic site to compare with the 5-HT4 agonist mosapride citrate (100 μmol/l) (applied for patent) applied locally and orally. Unlike mosapride, fluvoxamine failed to promote the regeneration of the nerve fiber tract across the anastomosis. Furthermore, fluvoxamine did not generate anti-distal-less homeobox 2 (DLX2)- and anti-SR4-positive cells (neural stem cells) and/or anti-neurofilament (NF)-positive cells (neural cells) in newly formed granulation tissue at the anastomosis, whereas these cell types were observed in mosapride-treated preparations. In contrast to its effects in guinea pigs, mosapride generated 5-bromo-2′-deoxyuridine (BrdU)-positive neural cells in ganglia sites 3 mm oral and anal from the anastomosis 2 wk after nerve fiber injury. All actions of mosapride were observed after local and or oral applications. These findings indicate that local SSRI treatment does not induce in vivo nerve fiber tract growth across the anastomosis in the rat distal gut. Mosapride induces nerve fiber tract growth across the anastomosis, mediated through enteric neural stem cells possibly from neural crest-derived stem cells or mesenchymal stem cells in the bone marrow.

scholarly journals Pluripotency and nuclear reprogramming

2008 ◽  
Vol 363 (1500) ◽  
pp. 2079-2087 ◽  
Author(s):  
Shinya Yamanaka
Keyword(s):  
Stem Cells ◽  
Molecular Mechanisms ◽  
Potential Problem ◽  
Somatic Cells ◽  
Embryonic Stem ◽  
Donor Cell ◽  
Human Embryos ◽  
Cell Sources ◽  
Cell Transplantation Therapy ◽  
Transplantation Therapy

Embryonic stem cells are promising donor cell sources for cell transplantation therapy, which may in the future be used to treat various diseases and injuries. However, as is the case for organ transplantation, immune rejection after transplantation is a potential problem with this type of therapy. Moreover, the use of human embryos presents serious ethical difficulties. These issues may be overcome if pluripotent stem cells are generated from patients' somatic cells. Here, we review the molecular mechanisms underlying pluripotency and the currently known methods of inducing pluripotency in somatic cells.

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