Dissertations / Theses on the topic 'Neurospheres'
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Leedale, Joseph. "Modelling HIF-1α dynamics within single cells and neurospheres." Thesis, University of Liverpool, 2013. http://livrepository.liverpool.ac.uk/15693/.
Full textOgita, Hideaki. "Transplantation of bone marrow-derived neurospheres into guinea pig cochlea." Kyoto University, 2010. http://hdl.handle.net/2433/120598.
Full textWetzig, Andrew R., and n/a. "Olfactory Stem Cells From Adult Rats." Griffith University. School of Biomolecular and Biomedical Science, 2007. http://www4.gu.edu.au:8080/adt-root/public/adt-QGU20070724.121953.
Full textWetzig, Andrew R. "Olfactory Stem Cells From Adult Rats." Thesis, Griffith University, 2007. http://hdl.handle.net/10072/366121.
Full textThesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Biomolecular and Biomedical Sciences
Faculty of Science
Full Text
Chakrabarty, Koushik. "Neuronal activation of Ras promotes enhancement and stabilization of dopaminergic properties in differentiating neurospheres /." Bochum, 2005. http://deposit.ddb.de/cgi-bin/dokserv?idn=980299659.
Full textMarshall, Gregory Paul. "Neurospheres and multipotent astrocytic stem cells neural progenitor cells rather than neural stem cells /." [Gainesville, Fla.] : University of Florida, 2005. http://purl.fcla.edu/fcla/etd/UFE0010047.
Full textTypescript. Title from title page of source document. Document formatted into pages; contains 97 pages. Includes Vita. Includes bibliographical references.
FRATTINI, VERONIQUE. "FOXP3, a novel glioblastoma oncosuppressor, affects proliferation and migration." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2013. http://hdl.handle.net/10281/40134.
Full textTiar, Feriel. "Développement d'un nouveau modèle orthotopique de glioblastome humain chez la souris." Thesis, Grenoble, 2013. http://www.theses.fr/2013GRENV078.
Full textGlioblastoma is the most common and aggressive subtype of brain tumors. Despite a better understanding of the disease and also the emergence of new therapeutic targets and strategies, the prognosis of patients remains unchanged. The failure to extrapolate preclinical results to the clinics highlights the complex nature of the disease and the importance of appropriate and predictive animal models for the study of new therapies. A pertinent animal model should be able to reproduce the characteristic of the human pathology in terms of disease development pattern, histological and transcriptomic specification, drug failure as well as diagnostic features. In this work, we developed a novel orthotopic mouse model derived from human glioblastoma spheres. Like in clinics, conventional MRI techniques and radiographic criteria were used to characterize tumor growth and treatment response to temozolomide. MRI findings have been completed and/or confirmed by histological examination and transcriptomic studies. Like clinically encountered tumors, this new orthotopic tumor model presents an infiltrating growth pattern, resistance to temozolomide and a molecular signature associated with histological features. In addition, this tumor model is characterized by a dynamic signaling pathway, which promotes cell invasion and migration as well as resistance to apoptosis and consequently to treatment. Thus, this preclinical model mimics clinical features of human glioblastoma and has a median host survival time of 82 days, which would be relevant in the assessment of preclinical therapies
Almeida, Thiago Lins da Costa. "Expressão dos genes EGFR, PTEN, MGMT e IDH1/2 e dos microRNAs miR-181b, miR-145, miR-149 e miR128a em neuroesferas em linhagens de glioblastoma submetidos ao tratamento com radiação ionizante e temozolomida." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/17/17137/tde-04012017-165133/.
Full textIntroduction: Glioblastoma multiforme is the most prevalent primary malignant neoplasm of the central nervous system. It has increased its incidence, while the overall survival remains over 14 months. Objectives: This study aims to evaluate the expression of the following genes EGFR, PTEN, MGMT and IDH1/2 and microRNAs miR-181b, miR-145, miR-149 and miR-128a in adhered cells (AC) and neurospheres (NS) from cell lines (T98G and U343) which were submitted to temozolomide (TMZ) and ionizing radiation (IR), isolated and associated (TMZ + IR). Methods: The cell lines T98G and U343 were treated with TMZ, IR and TMZ+IR. The analysis of gene expression and miRNAs was performed using the PCR in real time. Results: This study demonstrated: a) an improvement in the expression of IDH1 after IR (4-fold) and TMZ + IR (5-fold) in the NS (T98G); increased expression of IDH2 (20-fold) in the NS (T98G) after TMZ and IDH2 (3-fold) in AC (U343) submitted to TMZ + IR; b) reduction in EGFR expression after TMZ; increase this expression in NS (T98G) after IR (2-fold) and TMZ + IR (3-fold), and a decrease in AC (U343) submitted to TMZ and TMZ + IR; c) reduction in PTEN expression in NS (T98G) after TMZ and IR, and its improvement in NS (3-fold) when compared to TMZ + IR; d) increase in the expression of MGMT in NS (T98G) in IR groups (10-fold) and TMZ + IR (25-fold). It was also identified the expression of miRNAs results as: a) AC (U343) expressed more miR-181b after TMZ (60-fold), IR (20-fold) and TMZ + IR (40-fold); and miR- 128a improved after TMZ (500-fold), IR (200-fold) and TMZ + IR (600-fold); b) NS (T98G) after TMZ + IR expressed: miR-181b (30-fold); miR-149 (40-fold); miR-145 (300-fold) and miR-128a (40-fold); c) NS (U343) after IR huge expressed miR-149 and miR-145 (both in 4000-fold). Conclusion: IR was an independent and determining radio resistance factor in NS. However, we observed no complementarity action of oncomiRs regulation. This is the first study in the literature correlating gene expression, and miRNAs through TMZ, IR and IR + TMZ interventions in AC and NS.
Kannappan, Vinodh. "Investigation of the anticancer activity and molecular mechanisms of Disulfiram in Glioblastoma Multiforme." Thesis, University of Wolverhampton, 2015. http://hdl.handle.net/2436/600922.
Full textGodoy, Paulo Roberto D'Auria Vieira de. "Efeitos do Silenciamento de E2F1 e HEB, Fatores de Transcrição Preditos In Silico, em Células de Glioblastoma Irradiadas com Raios Gama." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/17/17135/tde-13062013-094602/.
Full textGlioblastoma multiforme (GBM) is one of the most lethal tumors, and radiation therapy remains one of the main treatments. New strategies are needed to suppress typical GBM treatment resistance and transcription factors (TFs) silencing seems to be a promising strategy. Our hypothesis is that TFs associated with lists of differentially expressed genes which were selected for irradiated compared to shamirradiated GBM cell lines, or GBM samples compared to brain tissue samples, could provide molecular targets that are supposed to increase tumor cell death when they are silenced. We analyzed proliferation, cell death and cell cycle progression, besides the formation and differentiation of neurospheres, using several analyses by flow cytometry. The TFs HEB and E2F1, whose primary functions are related to neurogenesis and cell proliferation, were selected from in silico analysis of GBM irradiated or sham-irradiated GBMs and GBM samples compared with normal brain samples, respectively. These TFs were found expressed in U87 GBM cell line, and primary astrocytes, as well as in neurospheres derivated from both, as analyzed by Western blot. Silencing of E2F1 and HEB in U87 cells, reduced proliferation, induced cell death and decreased the percentage of cells at G0/G1 (24, 48 or 72h) compared to the scrambled sequence transfected group. HEB and E2F1 silencing reduced the number of neurospheres when compared to cells transfected with scrambled sequence. Possibly, the anti-proliferative ability of silencing of HEB and E2F1 TFs observed in monolayer culture of U87, may act in neurospheres forming capacity and therefore may play a role in the maintenance of GBM stem cells. In our experiments, gene silencing did not alter the radio-resistance of U87 grown in monolayer. Irradiation did not reduce the number of neurospheres silenced for HEB compared to non-irradiated group, but reduced the number of cells present in neurospheres, indicating a possible role of HEB in response to ionizing irradiation in neurospheres, a fact that was not described yet. The silencing of E2F1 in neurospheres did not affect the response to irradiation. The expression of CD133, as assessed at eight days after the dissociation of cells silenced for E2F1 and HEB (cultured in differentiation culture media), was superior compared with the scrambled group, indicating a possible decrease in cell differentiation. The silencing of both TFs did not influence the positive selection of CD133 after irradiation, as observed in the group of neurospheres transfected with scrambled sequence, and irradiated compared to nonirradiated. Thus, E2F1 and HEB proved to be interesting targets for decreasing proliferation in both U87 cells grown as monolayer or neurospheres.
Balducci, Elisa. "Effect of DYRK1A dose reduction on the transcriptome of the developing mouse cerebral cortex : implications in gliogenesis." Doctoral thesis, Universitat Pompeu Fabra, 2012. http://hdl.handle.net/10803/85057.
Full textL’escorça cerebral és essencial per dur a terme les funcions més complexes en els mamífers. Entendre el procés de desenvolupament involucrat en la generació i el funcionament de les poblacions cel·lulars de l’escorça representa un dels principals camps d’investigació de la neurobiologia. DYRK1A és un gen sensible a dosis involucrat en el neurodesenvolupament i molt possiblement en la corticogènesis. En aquest estudi demostrem que la reducció de la dosi gènica de Dyrk1a en ratolí (Dyrk1a+/-) provoca una alteració substancial del transcriptoma de l’escorça cerebral neonatal que es principalment la conseqüencia de un retard en el l’expresió seqüencial dels gens durant el desenvolupament. També hem demostrat que els progenitors neuronals dels ratolins Dyrk1a+/- tenen una menor capacitat d’autorenovació i diferenciació en cèl·lules oligodendroglials in vitro. El estat epigenetic dels gens glials S100b i Gfap es troba alterat en l’escorça d’embrions a posicions especifiques del promotor abans de l’inici de la gliogènesis, suggerint que els progenitors neuronals de ratolins Dyrk1a+/- podrien tenir un potencial astrogliogènic incrementat i un potencial oligodendrogènic disminuït in vivo. En concordança, l’escorça de ratolins Dyrk1a+/- neonatals presenta un major número de progenitors oligodendroglials S100b+, mentres que el número d’astròcits Gfap+ es troba incrementat en ratolins Dyrk1a+/- adults. Finalment, hem demostrat que la vaina de mielina dels axons del cos callos i del nervi òptic i ciàtic es troba significativament reduïda en els ratolins Dyrk1a+/- adults, fet que indica una posible implicació de Dyrk1a en mielinització. En conjunt els nostres resultats indiquen que la baixada de dosi de Dyrk1a altera el potencial de diferenciació dels progenitors embrionaris de l'escorça i suggereix un nou paper de Dyrk1a en el desenvolupament i en la funcionalitat glial.
Chen, Xiaoli. "Investigation of adult corneal limbal neurosphere cells : a potential autologous cell resource for retinal repair." Thesis, University of Southampton, 2012. https://eprints.soton.ac.uk/376882/.
Full textKato, Takeo. "A neurosphere-derived factor, cystatin C, supports differentiation of ES cells into neural stem cells." Kyoto University, 2006. http://hdl.handle.net/2433/135642.
Full textMihaliak, Alicia M. "Clinically Relevant Doses of Chemotherapy Drugs Selectively and Reversibly Block Glioblastoma Neurosphere Proliferation in vitro: A Dissertation." eScholarship@UMMS, 2010. https://escholarship.umassmed.edu/gsbs_diss/492.
Full textIqbal, Jamila. "Cell model for genetic parkinsonism: Can cytological profiling using human olfactory neurosphere derived cells inform the mechanisms of neurodegeneration?" Thesis, Griffith University, 2018. http://hdl.handle.net/10072/384293.
Full textThesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Environment and Sc
Science, Environment, Engineering and Technology
Full Text
Cuddon, Paul. "The role of Ca²⁺ influx in neuronal cell growth and function : a study of hippocampal neurons and neurosphere-derived cells." Thesis, University of Cambridge, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.615262.
Full textSecomandi, Eleonora. "High expression of lysosomal cathepsin D inhibits neuroblastoma cell growth, migration and invasion, and confers better prognosis in neuroblastoma patients." Doctoral thesis, Università del Piemonte Orientale, 2022. http://hdl.handle.net/11579/144259.
Full textWirta, Valtteri. "Mining the transcriptome - methods and applications." Doctoral thesis, Stockholm : School of Biotechnology, Royal Institute of Technology, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-4115.
Full textWang, Dongdong. "Natural Product Chemical Probe Discovery against Parkinson’s Disease." Thesis, Griffith University, 2016. http://hdl.handle.net/10072/367616.
Full textThesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Natural Sciences
Science, Environment, Engineering and Technology
Full Text
Ichwan, Muhammad. "The identification of compounds from apples that regulate adult hippocampal neurogenesis." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2016. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-201069.
Full textEine Ernährung die täglich reich an Obst und Gemüse ist, hat insbesondere bei älteren Menschen einen positiven Einfluss auf kognitive Fähigkeiten. Pflanzeninhaltsstoffe wirken als natürliche Antioxidantien, indem sie oxidative Stressoren neutralisieren. Weiterhin beeinflussen pflanzliche Nährstoffe molekulare Signalwege welche beim Überleben von Neuronen eine Rolle spielen. Die adulte hippocampale Neurogenese ist ein dynamischer, lebenslanger Prozess, bei dem aus Vorläuferzellen funktionelle neue Neuronen in der Körnerzellschicht des Gyrus dentatus gebildet werden. Dieser Prozess trägt zur Plastizität des Gehirns bei und spielt eine bedeutende Rolle beim Lernen und für das Gedächtnis. Externe Stimuli wie zum Beispiel eine reizreiche Umgebung und körperliche Aktivität wirken als positive Regulatoren und begünstigen die adulte hippocampale Neurogenese. Welche Rolle die Ernährung dabei spielt und ob Nahrungsbestandteile einen proneurogenen Effekt auf adulte hippocampale Vorläuferzellen haben ist kaum bekannt. In diesem Projekt habe ich den Effekt von Nahrungsbestandteilen aus Äpfeln, welche eine bedeutende Quelle von pflanzlichen Nährstoffen in unserer Ernährung darstellen, auf die adulte hippocampale Neurogenese untersucht. Ich habe gezeigt, dass Querzetin, das am reichlichsten in Äpfeln enthaltende Polyphenol, in der Monolayer-Zellkultur den Austritt aus dem Zellzyklus induziert und die Differenzierung von adulten hippocampalen Vorläuferzellen fördert. Des Weiteren steigert Querzetin nach der Differenzierung in vitro die Anzahl an überlebenden Zellen. Dies geschieht durch die Aktivierung von endogenen Antioxidantien des Nrf2-Keap1-Signalweges und des für das Überleben von Zellen förderlichen Akt-Signalweges. Die Verabreichung von Querzetin in vivo als Nahrungsergänzungsmittel führte ebenfalls zu einem signifikanten Anstieg der Anzahl an überlebenden Zellen und neu gebildeten Nervenzellen im Gyrus dentatus. Um weitere potentiell aktive Wirkstoffe von Äpfeln zu bestimmen, habe ich eine Bioassay-ausgerichtete Fraktionierung durchgeführt, wobei der Fruchtfleischextrakt von Äpfeln der Sorte Pinova einer Fest-/ Flüssig-Separation unterzogen wurde. Die aktive Fraktion wurde anhand der primären Neurosphäre-Assay-Methode mit Zellen aus dem Gyrus dentatus adulter Mäuse ermittelt. Mittels spektrometrischer Analyse habe ich gezeigt, dass die aktiven Wirkstoffe im Fruchtfleischextrakt von Äpfeln zur Gruppe der Dihydroxybenzol-Glykosiden gehören, welche den nicht-flavonoiden Benzoesäure-Derivaten zuzuordnen sind. Im in vitro Neurosphäre-Assay habe ich zudem gezeigt, dass die Isomere dieser Wirkstoffe, die 2,3- und die 3,5-Dihydroxybenzoesäuren, die Anzahl der Neurosphären signifikant erhöhen. Interessanterweise ist die 3,5-Dihydroxybenzoesäure ein Agonist des Laktatrezeptors Hydroxycarboxylic acid receptor 1 (HCAR1) und weist sogar eine noch höhere Affinität als Laktat auf. Es wird suggeriert, dass dieser Rezeptor neurotrophische Wirkungen vermittelt, wie zum Beispiel eine erhöhte Produktion von BDNF und dessen Ausschüttung. Zudem habe ich das Vorkommen dieses Reporters erstmalig bei adulten hippocampalen Vorläuferzellen nachgewiesen. Um zu untersuchen, ob der Konsum handelsüblicher Obstprodukte die adulte hippocampale Neurogenese beeinflusst, habe ich Mäusen Apfelsaft ad libitum verabreicht. Nach der Gabe von Apfelsaft sah ich keinen signifikanten Anstieg der Gesamtneurogenese und keine Verbesserung der Leistungsfähigkeit im Morris-Wasserlabyrinth-Test. Dies ist bedingt durch eine zu geringe Konzentration der aktiven Wirkstoffe im Apfelsaft wodurch die wirksame Konzentration im Körper nicht erreicht wird. Ich schlussfolgere, dass in Äpfeln potentielle pro-neurogene Inhaltsstoffe enthalten sind, welche die adulte hippocampale Neurogenese beeinflussen. Dies wird insbesondere durch die Aktivierung endogener antioxidativer Mechanismen und molekularer Signalwege vermittelt, die für das Überleben von Zellen von Bedeutung sind. Weitere Studien sind nötig, um zu bestimmen wie sich die Aktivierung von HCAR1 auf die adulte hippocampale Neurogenese auswirkt. Dies stellt einen potentiellen neuen Wirkmechanismus dar, welcher die gesundheitlichen Vorteile von Obst- und Gemüsekonsum belegt
Xiang, Rui, and 向睿. "Growth of neurospheres in a microfluidic device characterized with selective plane illumination microscopy." Thesis, 2014. http://ndltd.ncl.edu.tw/handle/64382508587472182686.
Full text國立陽明大學
生醫光電研究所
102
Abstract To observe and culture the 3-D biological sample is always big challenge in biological experimints.3-D biological sample is closer to real condition then 2-D. In our study, we used SPIM(selective plane illumination microscopy) which is a type of light sheet microscope to research the growth of neurospheres. neurospheres is a 3-D functional biological sample which are aggregated by a lot of single neural stem cells,and neurospheres have ability of self-renew,proliferationand also will differentiated to neuron,astrocytes and oligodendrocytes. SPIM provide a low phototoxity,fast image acquisitionand 3-D reconstruction by scanning Z axis. Because neural stem cells were cultured to a 3-D functional neurospheres,the proliferation of neorosphere is the basic of cell culture in 3-D environment.The feature of light sheet microscopy is that illumination light will in the vertical direction with detection objective,so we developed a microfluidics device which can provide a micro environment for neurospheres.In the end, we observed the growth of cell in the 3 Days in the device and took the cell counting,demonstrated the relationship between the single neural stem cell and neurospheres. The thickness of beam waist is a key parameter of SPIM,we improve the illumination section by thinning the thickness of beam waist,promote the z resolution of system.The SPIM will be applied in the smaller scale biological sample.
Chakrabarty, Koushik [Verfasser]. "Neuronal activation of Ras promotes enhancement and stabilization of dopaminergic properties in differentiating neurospheres / Koushik Chakrabarty." 2006. http://d-nb.info/980299659/34.
Full textSYU, WEI-ZE, and 徐瑋澤. "The Neurospheres Induced from Adipose-Derived Stem Cells Combined With Acellular Biological Tissue Enhance Peripheral Nerve Repair." Thesis, 2019. http://ndltd.ncl.edu.tw/handle/spy9u6.
Full text國防醫學院
生命科學研究所
107
Abstract At present, the treatment of peripheral nerve injury has become more and more common. In addition to autologous nerve transplantation, there is no other kind of therapy available for the nerve defect of more than 3 cm. Acellular dermal matrix (ADM) has been widely used in the study of burns and scalds, and its extension and plasticity may be made into suitable nerve channels under different forms of nerve defects. Neural stem cells can now be used for peripheral nerve repair, but it is not easy to obtain. Adipose-derived stem cells (ADSC) are well-acquired, proliferative, and can differentiate into cells of different germ layers. It is assumed that ADSCs can be induced into a large number of neural stem cells and preserved, and neural stem cells can be decellularized. Survival on the tissue may help in the development of neural tissue engineering. The purpose of this dissertation is to use the ADM to incorporate neural stem cells (NSC) induced by ADSCs to establish neural tissue engineering. The focus of this study is that ADSCs can be induced into NSCs via growth factors, which can solve the source and quantity problems of NSCs. It was later confirmed that NSCs cultured on both ADM and ASN survived, and NSCs that survived on ADM also maintained markers of neural stem cells, and in animal experiments, ADM combined with NSC demonstrated improved ability to repair peripheral nerve defects. Importantly, in addition to providing new alternatives to peripheral nerve repair, ADM can be used to meet different forms of peripheral nerve defects in the future. Therefore, the exfoliation and plasticity of the ADM may be utilized and NSCs may be combined to treat different forms of nerve damage.
Osterberg, Nadja. "Induktion und Spezifikation serotonerger Neurone des ventralen Rhombencephalon der Maus." Doctoral thesis, 2009. http://hdl.handle.net/11858/00-1735-0000-0006-B67A-4.
Full textSantos, Tiago Luís Laundos dos. "Establisment of a Cell Culture System to Obtain Homogeneously Sized Neurospheres of Embryonic Stem Cell-derived Neural Stem/Progenitor Cells." Master's thesis, 2013. https://repositorio-aberto.up.pt/handle/10216/89938.
Full textSantos, Tiago Luís Laundos dos. "Establisment of a Cell Culture System to Obtain Homogeneously Sized Neurospheres of Embryonic Stem Cell-derived Neural Stem/Progenitor Cells." Dissertação, 2013. https://repositorio-aberto.up.pt/handle/10216/89938.
Full textBIDOLLARI, ERIS. "Neural stem cells differentiated from human induced pluripotent stem cells (iPSCs) as a novel in vitro model to study developmental pathways in Huntington Disease." Doctoral thesis, 2017. http://hdl.handle.net/11573/1058534.
Full textYu-Fang, Huang, and 黃郁芬. "Effects of SHP-2 on neurosphere cells development." Thesis, 2007. http://ndltd.ncl.edu.tw/handle/52357735452231263944.
Full text國防醫學院
生物及解剖學研究所
95
The nontransmembrane protein tyrosine phosphatase SHP-2 is widely distribution and implicates in cell growth and development. The previous study demonstrated that SHP-2 could express in neural precursor and glial cells. However, little know about SHP-2 subcellular localization in CNS precursor cells and differential cells including glial cells and neuron. This study was aimed to investigate the subcellular localization of SHP-2 in CNS precursor cells and terminal differentiation cells and to determine the role of SHP-2 on neurosphere cell development. We use immunocytochemistry and Western blot analysis to identify the expression of SHP-2 in neurosphere cells. We found phosphorylated SHP-2 expressed in focal adhesions of neural precursor cells, astrocytes and neurons. On activation, SHP-2 might recruit to focal adhesions, suggesting involvement of neurosphere cell adhesion and motility. We used protein tyrosine phosphatase inhibitor IV to block SHP-2 function to observe the role of SHP-2 involved in neurosphere cell spreading and migration. The results showed that neurosphere cell migration was decreased and the morphology of neuron and astrocyte was also changed. Taken together, SHP-2 might translocation to focal adhesions in response to integrin-mediated neural precursor cell adhesion, and thereby facilitate regulation of focal adhesion assembly/disassembly, cytoskeletal reorganization and cell migration by SHP-2.
Shih-YuLu and 陸詩羽. "Role of Fibroblast Growth Factor 9 in Neurosphere Formation of Adipose-derived Stem Cells." Thesis, 2017. http://ndltd.ncl.edu.tw/handle/ncpa65.
Full text國立成功大學
細胞生物與解剖學研究所
105
Adipose-derived stem cells (ASCs) were an ideal cell source for stem cell therapy can promote nerve regeneration after injury. The fibroblast growth factor 9 (FGF9) can alter the proliferation and cell-fate decision in stem cells. In my project, we aim to investigate the role of FGF9 during neurosphere formation of ASCs. We used chitosan- coated dish to culture ASCs to induce sphere formation with or without addition of FGF9. The expression of gene was detected by PCR and the protein expression level was observed by Western blot and IF staining. Besides, we investigated the involvement of potential signaling pathway of FGF9 signaling during the sphere formation using specific inhibitors or shRNA. The results showed the spheres formed by ASCs containing both neuronal and glial lineage cells. Addition of FGF9 induced spheres differentiation into Schwann lineage cells. Then, the activation of Akt, ERK signal pathway was decreased after forming the sphere and the inactivation of signal pathway was necessary for sphere formation. However, the phosphorylation of Akt pathway was transiently preserved by FGF9. Furthermore, the involvement of Akt signaling was confirmed by blockage of Akt signaling. The FGFR2 and 3 blocking antibody and shFGFRs was used to block FGFRs to investigate the major FGFR of FGF9 induced Schwann cell differentiation. The expression of Schwann cell markers induced by FGF9 was decreased when knockdown FGFR2. The result suggested that FGF9 could modulate NLC differentiation by activating Akt signaling via binding with FGFR2 during sphere formation. The finding of current study may show the possibility of differentiating ASCs into desired neural lineage by modulating the level of FGF9 during sphere formation.
Chi, Cheng-Yu, and 紀承諭. "Effect of Selected Broad and Narrow Bandwidth Plasmonic Thermal Emitter Infrared Radiation on the Neurosphere Cell Features Expression." Thesis, 2012. http://ndltd.ncl.edu.tw/handle/35015995510144166414.
Full text國立臺灣大學
生醫電子與資訊學研究所
100
The purpose of this research is to investigate the infrared irradiation effect on the cell growth and cell physiology of neonatal mice brain cell expression. The plasmonic thermal emitter with broad bandwidth (3~5 μm) and specific emission waveband were designed and used to irradiate the cells for 7 days in order to identify the specific wavelength that induces the cell expression the most significant. Infrared emitters used in this study are fabricated based on the theory of surface plasmon. The purpose of the second experiment is to understand the effect of narrow band infrared irradiation with 3.5, 4.0, and 4.5 μm wavelengths on cell growth features. The heat is generated by inputting electric current to the molybdenum film on silicon substrate. The infrared source can be achieved by heating the triple layer structure which consists of a SiO2 layer between two Ag films on the molybdenum, it is called metal/dielectric/metal (MIM) structure. The top Ag layer is perforated by periodic holes array, and the emission wavelength can be altered and selected by changing the lattice constant and diameter of the holes arrays. By metabolomics analysis, it is found that the mitochondria in the cell tend to follow the glycolysis pathway which can be benefit to the cell growth. It is observed that after illumination by PTE with peak wavelength at 4.0μm, the cell exhibits the largest response and cell number increased up to 45%. The experiments indicate that the cell number can be enhanced and tend to form neurospheres after infrared illumination. The study shows that IR illumination can improve the cell growth and points to new possibilities for future research.
Yuan-YuHsueh and 薛元毓. "Functional recoveries of sciatic nerve regeneration by combining chitosan-coated conduit and neurosphere cells induced from adipose-derived stem cells." Thesis, 2015. http://ndltd.ncl.edu.tw/handle/s5cdqb.
Full text國立成功大學
臨床醫學研究所
103
Peripheral nerve injuries are a significant source of disability. Although adherence to well-established basic principles of evaluation and repair can optimize results, clinical outcomes of peripheral nerve injuries are often suboptimal. The stem cell therapy of neural progenitor cell (NPC) from adipose-derived stem cell (ASC) may bring hope to peripheral nerve injury, especially in the clinical reality of tissue shortage. Transdifferentiation can be induced from ASC to NPC by adding numerous neurotrophic factors, or by mechanical microenvironment such as chitosan surface coating. To our knowledge, chitosan has widely been used for drug release and 3-dimentional scaffold for tissue engineering. And owning to the characteristics of biodegradable and biocompatible in nature, it also applies as nerve conduit to guide nerve regeneration. In author’s previous study, transdifferentiation of ASC into NPC can be achieved by using chitosan surface coating as the 3-D scaffold. Under the consideration of slow nature of nerve regeneration, continued maintenance of the microenvironment for the NPC seems possible to achieve by combined use of the chitosan conduit with induced NPC from ASC. The purpose of this study is to use the in vivo rat model of sciatic nerve transection to survey the therapeutic benefit of chitosan coated conduit containing with induced NPC from ASC. For the analysis of functional recoveries, we will focus on the improvement of the walking track analysis, relative gastrocnemius muscle weight measurement, and the ratio of regenerated myelinated axons. For the exploration of underlying mechanism, we will try to investigate the survival of functional cells after treatment, including the inflammatory profile.
HEIL, CONSTANTIN. "One size does not fit all: Cell type specific tailoring of culture conditions permits establishment of divergent stable lines from murine cerebellum." Doctoral thesis, 2014. http://hdl.handle.net/11573/888607.
Full textThe in vitro study of neural progenitors is based around the idea that defined culture conditions can emulate an environment which maintains an undifferentiated state and self-renewal capability of explanted progenitor cells, culminating in the growth of neurospheres. SHH signaling is a key signaling pathway with roles in morphogenesis and cell proliferation in the central nervous system, in particular, involved in mitogenic signaling within the context of postnatal cerebellar granule cell expansion. We demonstrate that in addition to commonly used mitogens such as EGF and bFGF, the SHH pathway agonist SAG, as well as genetic activation of SHH signaling by PTCH1 deletion, can lead to the growth of neurospheres from postnatal day 7 (p7) cerebellar explants. Interestingly, SAG derived cultures, termed murine SAG dependent spheres (mSS), can be generated solely from the p7 cerebellum and not from the sub-ventricular zone, a confirmed source of neurospheres derived by growth factors. Further, mSS cultures expressed ZIC1, ATOH1 and NESTIN, indicating that their identity is of the cerebellar granule cell progenitor (GCP) lineage. Strikingly, mSS cells can be maintained indefinitely in culture, as demonstrated by extensive clonogenic capability, assayed over a period of ten weeks. In the context of self-renewal, we assay gene expression of POU3f2, POU5f1, NANOG, and SOX2, genes associated with neural progenitors, which we find expressed in mSS cells. Importantly, mSS cultures are continuously dependent on SAG for their clonogenic potential and SHH pathway activation, assayed by expression of GLI1, PTCH1 and NMYC. In addition to the aforementioned extensive self-renewal capability mSS neurosphere cultures also maintain the ability to differentiate. In vitro differentiation leads to formation of cells with typical granule cell morphology and which are positive for beta3-tubulin, as assayed by western blot and immunofluorescence. Additionally, differentiated mSS cells display up-regulation of the cerebellar granule expressed gene GABRA6. Our work demonstrates that by applying culture conditions which are tailored towards biological characteristics of specific regions of the central nervous system the paradigm of the neurosphere can be expanded to include lineages not previously studied in this way. In particular, we apply this principle to unmask the property of cells from the GCP lineage as having extensive self-renewal capability in vitro.
Vaugeois, Alexandre. "Les cytokines inflammatoires modulent la prolifération et la différenciation in vitro des cellules souches/progénitrices de la moelle épinière." Thèse, 2013. http://hdl.handle.net/1866/12747.
Full textGrégoire, Catherine-Alexandra. "Mechanisms underlying activation of neural stem cells in the adult central nervous system." Thèse, 2016. http://hdl.handle.net/1866/15972.
Full textAt the end of the 19th century, Dr. Ramón y Cajal, a scientific pioneer, discovered that the nervous system was composed of individual cellular elements, later called neurons. He also noticed the complexity of this system and mentioned the impossibility of new neurons to be integrated into the adult nervous system. One of his famous quotes: “In adult centers the nerve paths are something fixed, ended, immutable. Everything may die, nothing may be regenerated” is representative of the prevalent dogma at the time (Ramón y Cajal 1928). Key studies conducted in the 1960-1970s suggested a different point of view. It was demonstrated that new neurons could be born during adulthood, but this discovery created an omnipresent skepticism in the scientific community. It took 30 years for the concept of adult neurogenesis to become widely accepted. This discovery, along with more advanced techniques, opened doors to potential therapeutic avenues for neurodegenerative diseases. Adult neural stem cells (NSCs) reside mainly in two niches in the brain: the subventricular zone of the lateral ventricles and the dentate gyrus of the hippocampus. Under normal conditions, neurogenesis level is relatively high in the SVZ whereas some steps are rate-limiting in the hippocampus. In contrast, the spinal cord is rather defined as a quiescent environment. One of the main questions that arose from these discoveries is: how do you activate adult NSCs in order to increase neurogenesis levels? In the hippocampus, environmental enrichment (including cognitive stimulation, exercise and social interactions) has been shown to promote hippocampal neurogenesis. The plasticity potential of this region is important as it could play a crucial role in rescuing learning and memory deficits. In the spinal cord, studies conducted in vitro demonstrated that ependymal cells found around the central canal have self-renewal and multipotency capacities (neurons, astrocytes, oligodendrocytes). Interestingly, it turns out that in vivo, following a spinal cord lesion, ependymal cells become activated, can self-replicate, but can only give rise to glia cell fate (astrocytes and oligodendrocytes). This new post-injury function shows that plasticity can still occur in a quiescent environment and could be exploited to develop endogenous spinal cord repair strategies. v As mentioned above, NSCs play important roles in normal brain function and neural repair following injury. However, little information is known about how a quiescent NSC becomes activated in order to perform these functions. The general objective of this project was to investigate the mechanisms underlying activation of neural stem cells in the adult central nervous system. My specific aims were to address this question using adult mice in two complementary models: 1) activation of hippocampal NSCs by environmental enrichment, and 2) activation of spinal cord NSCs by injury-induced neuroinflammation. Moreover, 3) to gain new insights into the molecular mechanisms of these models, we will perform transcriptomics studies to open new lines of investigation. The first project is expected to provide us with new insights into the basic cellular and molecular mechanisms through which environmental enrichment modulates adult brain plasticity. We first evaluated the contribution of individual environmental enrichment components to hippocampal neurogenesis (Chapter II). Voluntary exercise promotes neurogenesis, whereas a social context increases neuronal activation. We then determined the effect of these components on behavioural performances and transcriptome using an eight-arm radial maze to assess spatial memory, novel object recognition, and RNA-Seq, respectively (Chapter III). Runners show stronger spatial short-term memory recall, whereas mice exposed to social interactions had a better cognitive flexibility to abandon old memory. Surprisingly, RNA-Seq analysis indicated clear differences in the expression of modified transcripts between low runners and high runners, as well as for social interacting mice (within the complex environment). The second project consists of discovering how ependymal cells acquire NSC properties in vitro or multipotentiality following lesions in vivo. A RNA-Seq analysis revealed that the transforming growth factor-β1 (TGF-β1) acts as an upstream regulator of significant changes following spinal cord injury (Chapter IV). We therefore confirmed the presence of this cytokine after lesion and investigated its role on proliferation, differentiation, and survival of neurosphere-initiating cells from the spinal cord. Our results suggest that TGF-β1 regulates the acquisition and expression of stem cell properties of spinal cord-derived ependymal cells.
Bouab, Meriem. "L’effet du vieillissement sur les cellules souches neurales adultes." Thèse, 2010. http://hdl.handle.net/1866/4222.
Full textNeurogenesis persists throughout the adulthood in two regions of the mammalian central nervous system (SNC): the sub-ventricular zone (SVZ) of the forebrain and the sub-granular zone (SGZ) of the hippocampus. Neurogenesis is possible due to the proliferation capacity of stem cells present within both the SVZ and SGZ niches, but with aging, the forebrain undergoes a drastic reduction in its number of adult neural stem cells (aNSCs), a decrease of cell proliferation and an alteration of the neurogenic niches. However, a key unresolved question remains: how the onset of aNSC loss is temporally related to changes of proliferating activity and to structural alterations within the principal stem cell niche (the SVZ)? To gain insights into the initial events leading to aging-associated aNSC loss, we investigated the changes occurring to aNSCs and the SVZ niche between young adulthood and middle-age. The SVZ niche of middle-aged mice (12-months-old) was found to display reduced expression of markers for multiple neural precursor sub-populations when compared to young adult mice (2-months-old). Anatomically, this was associated with significant cytological aberrations, including an overall atrophy of the SVZ, loss of sub-ependymal cells, and accumulation of large lipid droplets within the ependyma. Functionally, these changes correlated with diminished SVZ activity and reduced number of newly born neurons reaching the principal target tissue: the olfactory bulbs. To determine whether changes were evident at the level of the SVZ stem cells, we evaluated key in vitro and in vivo parameters of aNSCs. Tissue culture experiments showed that equal numbers of neurosphere-forming aNSCs could be isolated from young adult and middle-aged forebrains. However, at middle-age, neural precursors seemed to be less sensitive to growth factors during their in vitro differentiation and displayed signs of increased quiescence in vivo. Collectively, these findings demonstrate that, with early aging, aNCS and their SVZ niche go through significant changes, and suggest that aging-associated aNSC loss is secondary to these events.