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Artykuły w czasopismach na temat "Neurospheres"

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Somredngan, Sirilak, Kasem Theerakittayakorn, Hong Thi Nguyen, Apichart Ngernsoungnern, Piyada Ngernsoungnern, Pishyaporn Sritangos, Mariena Ketudat-Cairns i in. "The Efficiency of Neurospheres Derived from Human Wharton’s Jelly Mesenchymal Stem Cells for Spinal Cord Injury Regeneration in Rats". International Journal of Molecular Sciences 24, nr 4 (14.02.2023): 3846. http://dx.doi.org/10.3390/ijms24043846.

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Spinal cord injury (SCI) causes inflammation and neuronal degeneration, resulting in functional movement loss. Since the availability of SCI treatments is still limited, stem cell therapy is an alternative clinical treatment for SCI and neurodegenerative disorders. Human umbilical cord Wharton’s jelly-derived mesenchymal stem cells (hWJ-MSCs) are an excellent option for cell therapy. This study aimed to induce hWJ-MSCs into neural stem/progenitor cells in sphere formation (neurospheres) by using neurogenesis-enhancing small molecules (P7C3 and Isx9) and transplant to recover an SCI in a rat model. Inducted neurospheres were characterized by immunocytochemistry (ICC) and gene expression analysis. The best condition group was selected for transplantation. The results showed that the neurospheres induced by 10 µM Isx9 for 7 days produced neural stem/progenitor cell markers such as Nestin and β-tubulin 3 through the Wnt3A signaling pathway regulation markers (β-catenin and NeuroD1 gene expression). The neurospheres from the 7-day Isx9 group were selected to be transplanted into 9-day-old SCI rats. Eight weeks after transplantation, rats transplanted with the neurospheres could move normally, as shown by behavioral tests. MSCs and neurosphere cells were detected in the injured spinal cord tissue and produced neurotransmitter activity. Neurosphere-transplanted rats showed the lowest cavity size of the SCI tissue resulting from the injury recovery mechanism. In conclusion, hWJ-MSCs could differentiate into neurospheres using 10 µM Isx9 media through the Wnt3A signaling pathway. The locomotion and tissue recovery of the SCI rats with neurosphere transplantation were better than those without transplantation.
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Blackwood, Christopher. "Quantitative approach to numbers and sizes: Generation of primary neurospheres from the dorsal lateral ganglionic eminence of late embryonic mice". F1000Research 8 (25.11.2019): 1983. http://dx.doi.org/10.12688/f1000research.21208.1.

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Background: The neurosphere assay is a powerful tool to study neural stem cell biology. The objective of this protocol is to create a simple and rapid approach to generate neurospheres from the dorsal lateral ganglionic eminence of late embryonic (day 17) mice. This method predicts the average number of neurospheres and provides an approximation of its expected size after 7 days in vitro. Characterization of numbers and sizes will provide investigators with quantitative data to advise on the implementation of downstream applications, including immnocytochemistry, self-renewal and differentiation assays. Methods: Our method is based on a simple dissection technique, where tissue surrounding the dorsal lateral ventricle from a single mouse embryo is trimmed away to enrich for neural stem cell and progenitor populations. Following this dissection, tissue is mechanically dissociated by trituration. Cells are then cultured in media containing epidermal growth factor and other supplements to generate healthy primary neurospheres. Results: Using this approach, we found reproducible number of primary neurospheres after 7 days in vitro. Furthermore, we found this method yields different sizes of neurospheres. Lastly, using an anti-GFAP antibody, we confirm that these neurospheres can be used for immunocytochemistry studies. Conclusions: Future use of this protocol provides metrics on the generation of neurospheres that will be useful for further advances in the area of stem cell biology.
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Blackwood, Christopher. "Quantitative approach to numbers and sizes: Generation of primary neurospheres from the dorsal lateral ganglionic eminence of late embryonic mice". F1000Research 8 (11.03.2020): 1983. http://dx.doi.org/10.12688/f1000research.21208.2.

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Background: The neurosphere assay is a powerful in vitro tool to investigate neural stem cells in the dorsal lateral ventricle (dLGE). In the dLGE, metrics of sizes and numbers of neurospheres generated using this assay has not been completely characterized. The objective of this protocol is to provide a stepwise method from a single isolation that predicts the average number of neurospheres generated and to estimate an approximation of its sizes after several days in vitro. The advantage of this protocol is that no expensive and specialized equipment is needed for tissue isolation. Estimates about the numbers and sizes of neurospheres will provide investigators with quantitative data to advise on how much starting dLGE tissue is required to generate the appropriate number of spheres for the implementation of downstream applications, including immunocytochemistry, self-renewal and differentiation assays. Methods: Our method is based on a simple dissection technique, where tissue surrounding the dorsal lateral ventricle from a single mouse embryo is trimmed away to enrich for neural stem cell and progenitor populations. Following this dissection, tissue is mechanically dissociated by trituration. Cells are then cultured in media containing epidermal growth factor and other supplements to generate healthy primary neurospheres. Results: Using this approach, we found reproducible number of primary neurospheres after 7 days in vitro (DIV). Furthermore, we observed that this method yields an average range of neurospheres sizes greater than 50 μm, but less than 100 μm after 7 DIV. Lastly, using an anti-GFAP antibody, we show that these neurospheres can be stained, confirming their use in future immunocytochemistry studies. Conclusions: Future use of this protocol provides metrics on the generation of primary neurospheres that will be useful for further advances in the area of stem cell biology.
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Tafreshi, Azita Parvaneh, Aude Sylvain, Guizhi Sun, Daniella Herszfeld, Keith Schulze i Claude C. A. Bernard. "Lithium chloride improves the efficiency of induced pluripotent stem cell-derived neurospheres". Biological Chemistry 396, nr 8 (1.08.2015): 923–28. http://dx.doi.org/10.1515/hsz-2014-0261.

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Abstract Induced pluripotent stem cell (iPSC)-derived neurospheres, which consist mainly of neural progenitors, are considered to be a good source of neural cells for transplantation in regenerative medicine. In this study, we have used lithium chloride, which is known to be a neuroprotective agent, in an iPSC-derived neurosphere model, and examined both the formation rate and size of the neurospheres as well as the proliferative and apoptotic status of their contents. Our results showed that lithium enhanced the formation and the sizes of the iPSC-derived neurospheres, increased the number of Ki67-positive proliferating cells, but reduced the number of the TUNEL-positive apoptotic cells. This increased number of Ki67 proliferating cells was secondary to the decreased apoptosis and not to the stimulation of cell cycle entry, as the expression of the proliferation marker cyclin D1 mRNA did not change after lithium treatment. Altogether, we suggest that lithium enhances the survival of neural progenitors and thus the quality of the iPSC-derived neurospheres, which may strengthen the prospect of using lithium-treated pluripotent cells and their derivatives in a clinical setting.
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Duval, Nathalie, Danielle Gomès, Viviane Calaora, Alessandra Calabrese, Paolo Meda i Roberto Bruzzone. "Cell coupling and Cx43 expression in embryonic mouse neural progenitor cells". Journal of Cell Science 115, nr 16 (15.08.2002): 3241–51. http://dx.doi.org/10.1242/jcs.115.16.3241.

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Embryonic neural progenitors isolated from the mouse striatal germinal zone grow in vitro as floating cell aggregates called neurospheres, which, upon adhesion, can be induced to differentiate into the three main cell types of the central nervous system (CNS), that is, astrocytes, neurons and oligodendrocytes. To study the possible role of connexins and junctional communication during differentiation of neural progenitors, we assessed cell-to-cell communication by microinjecting Lucifer Yellow into neurospheres at various times after adhesion. Cells located in neurospheres were strongly coupled, regardless of the differentiation time. Microinjections performed on the cell layers formed by differentiated cells migrating out of the neurosphere established that only astrocytes were coupled. These observations suggest the existence of at least three distinct communication compartments:coupled proliferating cells located in the sphere, uncoupled cells undergoing neuronal or oligodendrocytic differentiation and coupled differentiating astrocytes. A blockade of junctional communication by 18-β-glycyrrhetinic acid (βGA) reduced, in a concentration-dependent manner, the viability of undifferentiated neural progenitor cells. This effect appeared to be specific,inasmuch as it was reversible and that cell survival was not affected in the presence of the inactive analog glycyrrhyzic acid. Addition of βGA to adherent neurospheres also decreased cell density and altered the morphology of differentiated cells. Cx43 was strongly expressed in either undifferentiated or differentiated neurospheres, where it was found both within the sphere and in astrocytes, the two cell populations that were dye coupled. Western blot analysis further showed that Cx43 phosphorylation was strongly increased in adherent neurospheres, suggesting a post-translational regulation during differentiation. These results point to a major role of cell-to-cell communication and Cx43 during the differentiation of neural progenitor cells in vitro.
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Kühne, Britta Anna, Paula Vázquez-Aristizabal, Mercè Fuentes-Amell, Laura Pla, Carla Loreiro, Jesús Gómez-Catalán, Eduard Gratacós, Miriam Illa i Marta Barenys. "Docosahexaenoic Acid and Melatonin Prevent Impaired Oligodendrogenesis Induced by Intrauterine Growth Restriction (IUGR)". Biomedicines 10, nr 5 (23.05.2022): 1205. http://dx.doi.org/10.3390/biomedicines10051205.

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In this study, our aims were to characterize oligodendrogenesis alterations in fetuses with intrauterine growth restriction (IUGR) and to find therapeutic strategies to prevent/treat them using a novel rabbit in vitro neurosphere culture. IUGR was surgically induced in one uterine horn of pregnant rabbits, while the contralateral horn served as a control. Neural progenitor cells (NPCs) were obtained from pup’s whole brain and cultured as neurospheres mimicking the basic processes of brain development including migration and cell differentiation. Five substances, chosen based on evidence provided in the literature, were screened in vitro in neurospheres from untreated rabbits: Docosahexaenoic acid (DHA), melatonin (MEL), zinc, 3,3′,5-Triiodo-L-thyronine (T3), and lactoferrin (LF) or its metabolite sialic acid (SA). DHA, MEL and LF were further selected for in vivo administration and subsequent evaluation in the Neurosphere Assay. In the IUGR culture, we observed a significantly reduced percentage of oligodendrocytes (OLs) which correlated with clinical findings indicating white matter injury in IUGR infants. We identified DHA and MEL as the most effective therapies. In all cases, our in vitro rabbit neurosphere assay predicted the outcome of the in vivo administration of the therapies and confirmed the reliability of the model, making it a powerful and consistent tool to select new neuroprotective therapies.
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Hsu, Wesley, I.-Mei Siu, Gustavo Pradilla, Ziya L. Gokaslan, George I. Jallo i Gary L. Gallia. "Animal model of intramedullary spinal cord glioma using human glioblastoma multiforme neurospheres". Journal of Neurosurgery: Spine 16, nr 3 (marzec 2012): 315–19. http://dx.doi.org/10.3171/2011.11.spine11492.

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Object Advances in the diagnosis and management of patients with spinal cord tumors have been limited because of the rarity of the disease and the limitations of current animal models for spinal cord glioma. The ideal spinal cord tumor model would possess a number of characteristics, including the use of human glioma cells that capture the growth pattern and local invasive nature of their human counterpart. In this study, the authors' goal was to develop a novel spinal cord tumor model using a human neurosphere cell line. Methods Eighteen female athymic rats were randomized into 3 experimental groups. Animals in the first group (6 rats) received a 3-ml intramedullary injection containing DMEM and were used as controls. Animals in the second group (6 rats) received a 3-ml intramedullary injection containing 100,000 glioblastoma multiforme (GBM) neurosphere cells in 3 ml DMEM. Animals in the third group (6 rats) received a 3-ml intramedullary injection containing 9L gliosarcoma cells in 3 ml DMEM. Functional testing of hindlimb strength was assessed using the Basso-Beattie-Bresnahan (BBB) scale. Once the functional BBB score of an animal was less than or equal to 5 (slight movement of 2 joints and extensive movement of the third), euthanasia was performed. Results Animals in the GBM neurosphere group had a mean survival of 33.3 ± 2.0 days, which was approximately twice as long as animals in the 9L gliosarcoma group (16.3 ± 2.3 days). There was a significant difference between survival of the GBM neurosphere and 9L gliosarcoma groups (p < 0.001). None of the control animals died (p < 0.001 for GBM neurosphere group vs controls and 9L vs controls). Histopathological examination of the rats injected with 9L gliosarcoma revealed that all animals developed highly cellular, well-circumscribed lesions causing compression of the surrounding tissue, with minimal invasion of the surrounding gray and white matter. Histopathological examination of animals injected with GBM neurospheres revealed that all animals developed infiltrative lesions with a high degree of white and gray matter invasion along with areas of necrosis. Conclusions The authors have established a novel animal model of spinal cord glioma using neurospheres derived from human GBM. When injected into the spinal cords of athymic nude rats, neurospheres gave rise to infiltrative, actively proliferating tumors that were histologically identical to spinal cord glioma in humans. On the basis of their results, the authors conclude that this is a reproducible animal model of high-grade spinal cord glioma based on a human GBM neurosphere line. This model represents an improvement over other models using nonhuman glioma cell lines. Novel therapeutic strategies can be readily evaluated using this model.
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Raja, Waseem K., Esther Neves, Christopher Burke, Xin Jiang, Ping Xu, Kenneth J. Rhodes, Vikram Khurana, Robert H. Scannevin i Chee Yeun Chung. "Patient-derived three-dimensional cortical neurospheres to model Parkinson’s disease". PLOS ONE 17, nr 12 (1.12.2022): e0277532. http://dx.doi.org/10.1371/journal.pone.0277532.

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There are currently no preventive or disease-modifying therapies for Parkinson’s Disease (PD). Failures in clinical trials necessitate a re-evaluation of existing pre-clinical models in order to adopt systems that better recapitulate underlying disease mechanisms and better predict clinical outcomes. In recent years, models utilizing patient-derived induced pluripotent stem cells (iPSC) have emerged as attractive models to recapitulate disease-relevant neuropathology in vitro without exogenous overexpression of disease-related pathologic proteins. Here, we utilized iPSC derived from patients with early-onset PD and dementia phenotypes that harbored either a point mutation (A53T) or multiplication at the α-synuclein/SNCA gene locus. We generated a three-dimensional (3D) cortical neurosphere culture model to better mimic the tissue microenvironment of the brain. We extensively characterized the differentiation process using quantitative PCR, Western immunoblotting and immunofluorescence staining. Differentiated and aged neurospheres revealed alterations in fatty acid profiles and elevated total and pathogenic phospho-α-synuclein levels in both A53T and the triplication lines compared to their isogenic control lines. Furthermore, treatment of the neurospheres with a small molecule inhibitor of stearoyl CoA desaturase (SCD) attenuated the protein accumulation and aberrant fatty acid profile phenotypes. Our findings suggest that the 3D cortical neurosphere model is a useful tool to interrogate targets for PD and amenable to test small molecule therapeutics.
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Godoy, Paulo R. D. V., Ali Pour Khavari, Marzia Rizzo, Elza T. Sakamoto-Hojo i Siamak Haghdoost. "Targeting NRF2, Regulator of Antioxidant System, to Sensitize Glioblastoma Neurosphere Cells to Radiation-Induced Oxidative Stress". Oxidative Medicine and Cellular Longevity 2020 (16.06.2020): 1–17. http://dx.doi.org/10.1155/2020/2534643.

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The presence of glioma stem cells (GSCs), which are enriched in neurospheres, may be connected to the radioresistance of glioblastoma (GBM) due to their enhanced antioxidant defense and elevated DNA repair capacity. The aim was to evaluate the responses to different radiation qualities and to reduce radioresistance of U87MG cells, a GBM cell line. U87MG cells were cultured in a 3D model and irradiated with low (24 mGy/h) and high (0.39 Gy/min) dose rates of low LET gamma and high LET carbon ions (1-2 Gy/min). Thereafter, expression of proteins related to oxidative stress response, extracellular 8-oxo-dG, and neurospheres were determined. LD50 for carbon ions was significantly lower compared to LD50 of high and low dose rate gamma radiation. A significantly higher level of 8-oxo-dG was detected in the media of cells exposed to a low dose rate as compared to a high dose rate of gamma or carbon ions. A downregulation of oxidative stress proteins was also observed (NRF2, hMTH1, and SOD1). The NRF2 gene was knocked down by CRISPR/Cas9 in neurosphere cells, resulting in less self-renewal, more differentiated cells, and less proliferation capacity after irradiation with low and high dose rate gamma rays. Overall, U87MG glioma neurospheres presented differential responses to distinct radiation qualities and NRF2 plays an important role in cellular sensitivity to radiation.
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Zainal Abidin, Shahidee, Han-Chung Lee, Syahril Abdullah, Norshariza Nordin, Pike-See Cheah i King-Hwa Ling. "The expression profile of miR-3099 during neural development of Ts1Cje mouse model of Down syndrome". Neuroscience Research Notes 4, nr 1 (15.03.2021): 7–15. http://dx.doi.org/10.31117/neuroscirn.v4i1.62.

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MicroRNA-3099 (miR-3099) plays a crucial role in regulating neuronal differentiation and development of the central nervous system (CNS). The miR-3099 is a pro-neuronal miRNA that promotes neural stem/progenitor cell (NSPC) differentiation into neuronal lineage by suppressing astrogliogenesis. Down syndrome (DS) brain exhibited increased astrogliogenesis and reduced neuronal cell density. The involvement of miR-3099 in the neurodevelopment of DS has not been investigated and potentially responsible for the neurogenic-to-gliogenic shift phenomenon observed in DS brain. To investigate the role of miR-3099 during DS brain development, neural/progenitor cell proliferation and differentiation, we profiled miR-3099 expression level in the Ts1Cje, a mouse model for DS. We analysed the Ts1Cje whole brain at embryonic day (E) 10.5, E14.5 and P1.5, proliferating neurospheres and differentiating neurospheres at 3, 9 and 15 days in vitro (DIV). Expression of miR-3099 in both the developing mouse brain and the differentiating neurosphere was not significantly different between Ts1Cje and wild type controls. In contrast, the expression level of miR-3099 was significantly higher (p<0.05) in proliferating NSPC derived from the Ts1Cje compared to wild-type. Further molecular profiling of NPSC and glial cell markers indicated that the expression of Sox2 (p<0.01) and Gfap (p<0.05) were significantly downregulated in Ts1Cje neurospheres as compared to that of wild type, respectively. While there were no significant differences in Tuj1 and Nestin expression levels between the Ts1Cje and wild type neurospheres, their expression levels were ~3-fold upregulated and ~2.6 downregulated Ts1Cje group, respectively. The findings suggest that dysregulation of miR-3099 affects NSPC lineage commitment as indicated by altered postmitotic neuronal cell markers. Further molecular characterisation and gene expression profiling of other neuronal and glial markers will help refine the analysis of gene-gene interactions underlying the neuropathologies of DS.
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Rozprawy doktorskie na temat "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/.

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HIF-1 (Hypoxia Inducible Factor-1) is an oxygen-regulated transcription factor that mediates the intracellular response to hypoxia in human cells, targeting specific genes that promote cell survival by inducing processes such as angiogenesis and glycolysis. The HIF-1 signalling pathway has been of considerable interest due to its role in mammalian development and in particular several pathologies such as ischemia and cancer. Low cellular oxygen levels are found in cancer due to the rapid proliferation of tumour cells distant to blood vessels (forming a hypoxic core) and the typically irregular vasculature is unable to properly perfuse the tumour. In the Centre for Cell Imaging at the University of Liverpool, time lapsed imaging in an oxygen-controlled environment has captured the transient dynamics of the oxygen regulated subunit of HIF-1, HIF-1α, and revealed heterogeneity between individual cells. The essential characteristics of this data are modelled with a system of differential equations describing the feedback inhibition between HIF-1α and the pathway’s effective oxygen sensors. This novel model was formulated by employing a minimalist approach initially, allowing us to use the rich variety of single-cell data to determine the structure of the feedback loop between two key pathway components. Once the central regulatory motif was identified, the model was expanded to include more complexity, including experimental measurements for model parameter values and additional system components. Oxygen plays an especially important role in the early stages of tumour formation. Measurements of oxygen within cells have been recorded in cultured spheres of neuroblastoma cells at different atmospheric conditions. This data is representative of the early development stages of an avascular tumour and a spatial oxygen-diffusion model was coupled with the single-cell HIF-1α model to describe the dynamics of HIF-1α across a developing tumour. This coupled model is used to study HIF-1α dynamics in the context of various oxygen-dependent cellular functions such as cell-cycle progression and apoptosis by integrating with modifications of published mathematical models.
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Ogita, Hideaki. "Transplantation of bone marrow-derived neurospheres into guinea pig cochlea". Kyoto University, 2010. http://hdl.handle.net/2433/120598.

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Wetzig, Andrew R., i 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.

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The formation of neurospheres was important in demonstrating that neurogenesis in the adult brain may be fuelled by a stem cell population. The olfactory mucosa is another site of neurogenesis which, in humans, has been observed to contain a stem cell population through the formation of neurospheres (Murrell et al., 2005). Stem cells can be defined as cells capable of self-renewal and multipotency. The aim of this study was to investigate the potential of rat olfactory stem cells growing as neurospheres. The hypothesis is that the rat olfactory mucosa contains a 'true' stem cell population that can be cultured as neurospheres and that will demonstrate multipotency by differentiating into 'non-olfactory' cell types and possess the capacity for self-renewal, if provided with the appropriate environmental niche. Here it was found that adult rat olfactory mucosa is capable of generating neurospheres when cultured in EGF and bFGF. Evidence of self-renewal was provided by the formation of six generations of neurospheres, the formation of neurospheres from single cells and the expression of markers associated with self-renewal by neurosphere cells. The multipotency of olfactory neurosphere cells was demonstrated through manipulation of the stem cell niche. In defined culture conditions, extracellular matrix molecules and growth factors were able to induce the differentiation of neurosphere cells down the dopaminergic lineage pathway. When co-cultured with differentiating cells, neonatal myoblasts and 3T3-L1 cells, olfactory neurosphere cells were able to differentiate and incorporate into a skeletal muscle myotube and differentiate into adipocytes, respectively. In conclusion it was found that the adult rat olfactory mucosa is capable of generating neurospheres. When presented with an appropriate niche neurosphere cells are able to self-renew and demonstrate multipotency.
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Wetzig, Andrew R. "Olfactory Stem Cells From Adult Rats". Thesis, Griffith University, 2007. http://hdl.handle.net/10072/366121.

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The formation of neurospheres was important in demonstrating that neurogenesis in the adult brain may be fuelled by a stem cell population. The olfactory mucosa is another site of neurogenesis which, in humans, has been observed to contain a stem cell population through the formation of neurospheres (Murrell et al., 2005). Stem cells can be defined as cells capable of self-renewal and multipotency. The aim of this study was to investigate the potential of rat olfactory stem cells growing as neurospheres. The hypothesis is that the rat olfactory mucosa contains a 'true' stem cell population that can be cultured as neurospheres and that will demonstrate multipotency by differentiating into 'non-olfactory' cell types and possess the capacity for self-renewal, if provided with the appropriate environmental niche. Here it was found that adult rat olfactory mucosa is capable of generating neurospheres when cultured in EGF and bFGF. Evidence of self-renewal was provided by the formation of six generations of neurospheres, the formation of neurospheres from single cells and the expression of markers associated with self-renewal by neurosphere cells. The multipotency of olfactory neurosphere cells was demonstrated through manipulation of the stem cell niche. In defined culture conditions, extracellular matrix molecules and growth factors were able to induce the differentiation of neurosphere cells down the dopaminergic lineage pathway. When co-cultured with differentiating cells, neonatal myoblasts and 3T3-L1 cells, olfactory neurosphere cells were able to differentiate and incorporate into a skeletal muscle myotube and differentiate into adipocytes, respectively. In conclusion it was found that the adult rat olfactory mucosa is capable of generating neurospheres. When presented with an appropriate niche neurosphere cells are able to self-renew and demonstrate multipotency.
Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Biomolecular and Biomedical Sciences
Faculty of Science
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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.

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Marshall, 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.

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Thesis (Ph.D.)--University of Florida, 2005.
Typescript. Title from title page of source document. Document formatted into pages; contains 97 pages. Includes Vita. Includes bibliographical references.
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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.

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The transcription factor FOXP3, a master regulator of Treg cells has been proposed to function as a tumor suppressor in breast and prostate cancer. In the present study we provide evidence that FOXP3 is expressed in normal brain but strongly down-regulated in both primary and recurrent glioblastoma (GB) specimens and in corresponding cell lines growing in culture in the presence of mitogenic factors (mostly Epidermal Growth Factor - EGF and b-Fibroblast Growth Factor – bFGF) as neurospheres (NS). We also found that FOXP3 expression was higher in low-grade gliomas than in GB. Neurosphere generation, a feature present in 58% of the GB that we examined, correlated with lower expression of FOXP3 and shorter patient survival. Our main result refers to the contribution of FOXP3 expression in affecting proliferation and migration in vitro and in vivo. FOXP3 was silenced in one GB-NS expressing measurable levels of the gene. Intracranial injection of these GB-NS cells in nude mouse brains increased significantly tumor development and aggressiveness. Deriving gliomas showed a total absence of FOXP3 expression associated with a significant increase in proliferation and migration. Conversely, FOXP3 over-expression impaired GB-NS migration and proliferation in vitro. We also demonstrated using ChIP that FOXP3 is a transcriptional regulator of p21 and c-MYC supporting the idea that dysregulated expression of these factors is a major mechanism of tumorigenesis driven by the loss of FOXP3 expression in gliomas. These findings support the assertion that FOXP3 exhibits tumor suppressor activity in glioblastomas.
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Tiar, Feriel. "Développement d'un nouveau modèle orthotopique de glioblastome humain chez la souris". Thesis, Grenoble, 2013. http://www.theses.fr/2013GRENV078.

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Le glioblastome représente le sous-type de tumeur cérébrale le plus fréquent et le plus agressif. Malgré une meilleure compréhension de la maladie ainsi que l'émergence de nouvelles cibles, voire de nouveaux outils thérapeutiques, son pronostic reste inchangé. En effet, l'échec de l'extrapolation des résultats vers la clinique met en exergue la nature complexe de la maladie et la dimension décisive des modèles animaux adéquats et prédictifs dans l'étude des nouvelles thérapies. Et pour cause, un modèle animal idéal doit pouvoir reproduire les caractéristiques histo-pahologiques, génétiques et diagnostics de la pathologie humaine. Il doit avoir également une survie suffisante pour permettre la mise en place et l'évaluation de nouveaux traitements. Au cours de ce travail, nous avons développé un nouveau modèle de tumeur orthotopique chez la souris à partir de cellules de glioblastome humain cultivées en neurosphères. D'une façon similaire aux protocoles cliniques de neuro-imagerie, les techniques classiques d'IRM et les critères radiographiques ont été utilisés afin d'étudier la croissance tumorale de ce modèle ainsi que l'évaluation de sa réponse au traitement à base de temozolomide. Les observations par imagerie ont été complétées et/ou confirmées par examen histologique ainsi que par l'étude du transcriptome. Comme en clinique, ce nouveau modèle orthotopique présente une tumeur invasive et nécrotique, une résistance au temozolomide ainsi que des signatures moléculaires associées aux observations histologiques. De plus, ce modèle tumoral est caractérisé par une dynamique de signalisation promouvant l'invasion, la migration et la résistance à l'apoptose à l'origine de sa survie post-thérapeutique. Ainsi, ce modèle préclinique mime, au plus près, les caractéristiques de la pathologie humaine avec une médiane de survie des animaux de 82 jours, ce qui le rend pertinent pour l'évaluation préclinique des nouvelles stratégies thérapeutiques
Glioblastoma 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
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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/.

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Introdução: O glioblastoma multiforme é a neoplasia maligna primária mais prevalente do sistema nervoso central. Enquanto apresenta aumento em sua incidência, mantém a perspectiva de sobrevida global aproximada de 14 meses. Objetivos: O presente estudo objetiva avaliar a expressão dos genes EGFR, PTEN, MGMT e IDH1/2 e dos microRNAs miR-181b, miR-145, miR-149 e miR-128a em neuroesferas (NE) e células aderidas (CA), a partir das linhagens celulares (T98G e U343) submetidas ao tratamento com temozolomida (TMZ) e com radiação ionizante (RI) isolados e em associação (TMZ+RI). Material e métodos: As linhagens celulares T98G e U343 foram tratadas com TMZ, RI e TMZ+RI. A verificação da expressão dos genes e miRNAs foi realizada utilizando o método de PCR em tempo real. Resultados: Observamos: a) o aumento na expressão do IDH1 após RI (4-fold) e TMZ+RI (5-fold) nas NE (T98G); o aumento na expressão do IDH2 (20-fold) nas NE (T98G), após TMZ, e do IDH2 (3-fold) nas CA (U343) submetidas à TMZ+RI; b) a redução na expressão do EGFR após TMZ; o aumento dessa expressão nas NE (T98G), após RI (2-fold) e TMZ+RI (3-fold), e a sua diminuição nas CA (U343) submetidas à TMZ e TMZ+RI; c) a redução na expressão PTEN nas NE (T98G), após TMZ e RI, e sua expressão nas NE (3-fold) frente à TMZ+RI; d) aumento na expressão de MGMT nas NE (T98G) nos grupos RI (10-fold) e TMZ+RI (25-fold). Quanto a expressão de miRNAs, foram identificados os seguintes resultados: a) as CA (U343) expressaram: miR-181b após TMZ (60-fold), RI (20-fold) e TMZ+RI (40- fold); e miR-128a após TMZ (500-fold), RI (200-fold) e TMZ+RI (600-fold); b) as NE (T98G) após TMZ+RI expressaram: miR-181b (30-fold), miR-149 (40-fold), miR-145 (300-fold) e miR-128a (40-fold); c) as NE (U343) após RI hiperexpressaram miR-149 e miR-145 (ambos em 4000-fold). Conclusão: A RI apresentou-se como fator independente e determinante para a radiorresistência das NE, entretanto não observamos ação de complementariedade de regulação dos oncomiRs observados sobre a expressão dos genes estudados. Esta é a primeira análise na literatura que correlaciona a expressão de genes e de miRNAs através das intervenções TMZ, RI e TMZ+RI sobre células aderidas e neurosferas.
Introduction: 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.
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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.

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Glioblastoma Multiforme (GBM) is the most common lethal brain tumour associated with dismal survival rate. GBM is considered to be an incurable malignancy as these tumours evade all intricate attempts of therapy and no contemporary chemotherapeutic regimen is effective. Although the existence of cancer stem cells (CSCs) is still debatable, it is widely accepted that GBM has a small population of cells expressing CSC markers (~1%) that are highly resistant to chemo-radiation therapy. Recent evidence indicates that hypoxia induces cancer stem cell (CSC) phenotypes via epithelial-to-mesenchymal transition (EMT) that promote therapeutic resistance in solid tumours. Given that GBMs are extensively hypooxygenated heterogenous tumours, understanding the molecular relationship between hypoxia, biology of CSCs, EMT and chemoresistance would be invaluable for development of drugs that can target CSCs. Evidence suggests that hypoxia inducible factors (HIFs), NF-B and aldehyde dehydrogenase (ALDH) together orchestrate the stemness and chemoresistance in hypoxia induced CSCs. But the insights on the mechanisms still remain obscure. In this study we used an in vitro GBM CSC and hypoxia model along with NF-B-p65 and HIF transfected GBM cell lines to investigate the relationship between HIFs, NF-B activation and ALDH activity and their role in chemoresistance. The findings of this study demonstrated that GBM cells grown as spheres consist of a vast proportion of hypoxic cells with elevated CSC and EMT markers suggesting hypoxia induced EMT. GBM-CSCs are chemoresistant and displayed increased levels of HIFs, NF-B and ALDH activity. It was also observed that stable transfection of GBM cells with NF-B-p65 or HIFs induced CSC and EMT markers indicating their essential role in maintaining CSC phenotypes. The study also highlighted the importance of NF-B and ALDH in driving chemoresistance and the potential role of NF-B as the master regulator of hypoxia induced stemness in GBM cells. In this study, we used Disulfiram (DS), an anti-alcoholism drug, in combination with copper (Cu) to target the hypoxia-NF-B axis and inhibit ALDH activity to reverse chemoresistance in GBM CSCs. We showed that DS/Cu is cytotoxic to GBM cells and completely eradicated the resistant CSC population at low nanomolar levels in vitro. We also demonstrated that DS/Cu effectively inhibited GBM in vivo using newly formulated PLGA-DS nanoparticles. DS is an FDA approved drug with low/no toxicity to normal tissues and can freely pass through the blood brain barrier (BBB). Further study may lead to quick translation of DS into clinical trials.
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Książki na temat "Neurospheres"

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Dulchinos, Donald P. Neurosphere: The Convergence of Evolution, Group Mind, and the Internet. Red Wheel/Weiser, 2005.

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Neurosphere: The Convergence of Evolution, Group Mind, and the Internet. Weiser Books, 2005.

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Części książek na temat "Neurospheres"

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Marshall, Gregory P., Heather H. Ross, Oleg Suslov, Tong Zheng, Dennis A. Steindler i Eric D. Laywell. "Production of Neurospheres from CNS Tissue". W Neural Stem Cells, 135–50. Totowa, NJ: Humana Press, 2008. http://dx.doi.org/10.1007/978-1-59745-133-8_12.

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Bessa, Sílvia, Pedro Quelhas i Isabel F. Amaral. "Automatic Quantification of Cell Outgrowth from Neurospheres". W Pattern Recognition and Image Analysis, 141–48. Berlin, Heidelberg: Springer Berlin Heidelberg, 2013. http://dx.doi.org/10.1007/978-3-642-38628-2_16.

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Fritsche, Ellen, Kathrin Gassmann i Timm Schreiber. "Neurospheres as a Model for Developmental Neurotoxicity Testing". W Methods in Molecular Biology, 99–114. Totowa, NJ: Humana Press, 2011. http://dx.doi.org/10.1007/978-1-61779-170-3_7.

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Struckhoff, Amanda Parker, i Luis Del Valle. "Neurospheres and Glial Cell Cultures: Immunocytochemistry for Cell Phenotyping". W Neuronal Cell Culture, 119–32. Totowa, NJ: Humana Press, 2013. http://dx.doi.org/10.1007/978-1-62703-640-5_10.

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Parker Struckhoff, Amanda, i Luis Del Valle. "Neurospheres and Glial Cell Cultures; from Plating to Cell Phenotyping". W Neuronal Cell Culture, 131–45. New York, NY: Springer US, 2021. http://dx.doi.org/10.1007/978-1-0716-1437-2_9.

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Hameed, Liyakath Ali Shahul, i András Simon. "Isolation and Culture of Neurospheres from the Adult Newt Brain". W Methods in Molecular Biology, 197–204. New York, NY: Springer New York, 2015. http://dx.doi.org/10.1007/978-1-4939-2495-0_16.

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Sardá-Arroyo, Laura, Clarissa Schitine, Sara Alves Xapelli i Henning Ulrich. "Mice Post-natal Subventricular Zone Neurospheres: Derivation, Culture, Differentiation and Applications". W Working with Stem Cells, 79–96. Cham: Springer International Publishing, 2016. http://dx.doi.org/10.1007/978-3-319-30582-0_5.

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Lin, Ching-Hui, Hao-Chen Chang, Don-Ching Lee, Ing-Ming Chiu i Chia-Hsien Hsu. "Enzyme-Free Dissociation of Neurospheres by a Microfluidic Chip-Based Method". W Methods in Molecular Biology, 289–97. New York, NY: Springer New York, 2016. http://dx.doi.org/10.1007/7651_2016_348.

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Yu, Weimiao, Hwee Kuan Lee, Srivats Hariharan, Shvetha Sankaran, Pascal Vallotton i Sohail Ahmed. "Segmentation of Neural Stem/Progenitor Cells Nuclei within 3-D Neurospheres". W Advances in Visual Computing, 531–43. Berlin, Heidelberg: Springer Berlin Heidelberg, 2009. http://dx.doi.org/10.1007/978-3-642-10331-5_50.

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Bartmann, Kristina, Julia Hartmann, Julia Kapr i Ellen Fritsche. "Measurement of of Differentiated Human iPSC-Derived Neurospheres Recorded by Microelectrode Arrays (MEA)". W Neuromethods, 473–88. New York, NY: Springer US, 2021. http://dx.doi.org/10.1007/978-1-0716-1637-6_22.

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Streszczenia konferencji na temat "Neurospheres"

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Junqueira, Danielle, Juliana Nascimento, Daniel de Martins-de-Souza i Stevens Rehen. "Proteome analysis of neural stem cells and neurospheres infected with Zika Virus". W Congresso de Iniciação Científica UNICAMP. Universidade Estadual de Campinas, 2019. http://dx.doi.org/10.20396/revpibic2720191596.

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Wei Xiong, Shue-Ching Chia, Joo-Hwee Lim, S. Shvetha i S. Ahmed. "Detection of unstained living neurospheres from phase contrast images with very large illumination variations". W 2011 33rd Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE, 2011. http://dx.doi.org/10.1109/iembs.2011.6091520.

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Yang, Renyuan, Emily Kozik, Bhavika Patel, David Jiles, Donald Sakaguchi i Long Que. "Studies of Neurospheres Cultured Using Adult Hippocampal Progenitor Cells Under Off-Chip Magnetic Stimulation". W 2019 20th International Conference on Solid-State Sensors, Actuators and Microsystems & Eurosensors XXXIII (TRANSDUCERS & EUROSENSORS XXXIII). IEEE, 2019. http://dx.doi.org/10.1109/transducers.2019.8808481.

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Pellegatta, Serena, Barbara Savoldo, Chuang Su, Ferrone Soldano, Gaetano Finocchiaro i Dotti Gianpietro. "Abstract LB-249: Condroitin sulfate proteoglycan 4 (CSPG4)- redirected T cells eliminate glioblastoma-derived neurospheres". W Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/1538-7445.am2016-lb-249.

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Kashirina, Alena, Ekaterina D. Momotyuk, Evgeniya Bukina, Erdem B. Dashinimaev, Ekaterina A. Vorotelyak, Maria M. Lukina, Varvara V. Dudenkova i in. "Analysis of the metabolic and oxygen status of 3D neurospheres from iPSCs using FLIM / PLIM methods". W Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues XIX, redaktorzy James F. Leary, Attila Tarnok i Irene Georgakoudi. SPIE, 2021. http://dx.doi.org/10.1117/12.2577638.

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Xiong, Wei, Shue Ching Chia, Joo Hwee Lim, Hwee Kuan Lee, Shvetha Sankaran i Sohail Ahmed. "Segmentation of neural stem cells/neurospheres in high content brightfield microscopy images using localized level sets". W 2012 19th IEEE International Conference on Image Processing (ICIP 2012). IEEE, 2012. http://dx.doi.org/10.1109/icip.2012.6467283.

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Bockman, Matthew D., Igor I. Katkov, Stephen B. Jones, Vsevolod Katkov i Ilya Yakhnenko. "ComfortFreezer™: A Benchtop LN2–Free Programmable Freezer for Cryopreservation of Adherent Cells in Multi-Well Plates for Cell-Based High Content Screening". W ASME 2012 International Mechanical Engineering Congress and Exposition. American Society of Mechanical Engineers, 2012. http://dx.doi.org/10.1115/imece2012-85469.

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Human pluripotent stem cells (hPSCs) and their progeny such as hPSC-derived cardiomyocytes and neural cells hold great potential as a source for cell therapy and regenerative medicine, as well can be effectively used for high high content screening (HCS) of drug candidates and for toxicity tests. Cryopreservation (CP), storage, and shipment of the cells are key elements for eventual clinical, pharmaceutical and environmental applications, which will require large numbers of quality controlled and ready for use cells. Traditionally, the cells are frozen in suspensions of either fully dissociated cells) or loosely associated clusters such as clumps of hPSCs, clusters of beaters”of cardiomyocytes, (“or neurospheres of neural precursors. Beside logistical inconvenience for some applications such as HCS, additional manipulation with the cells (detachment, dissociation and centrifugation) can introduce substantial stress to the cells prior to freezing and after thawing, which per se may tremendously decrease the cell cryosurvival and functionality. Here, we are presenting ComfortFreezer™, a novel bench-top device specifically designed for cryopreservation in multi-well plates for cell-based high content screening (HCS), which combines a liquid-nitrogen (LN2) free programmable freezer This cryogenic equipemnt can bring serious advantage for HCS in drug screening, environmental toxicity evaluation, and other variety of HCS-based applications.
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Mueller, Claudius, Ana C. deCarvalho, Tom Mikkelsen, Laila Poisson, Valerie Calvert, Andrew Borgman, David M. Cherba, Mary E. Winn i Emanuel F. Petricoin. "Abstract 1213: Comparing protein pathway activation mapping portraits between gliobastoma patient-matched primary tumor, xenografts and neurospheres: implications for precision medicine". W Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA. American Association for Cancer Research, 2014. http://dx.doi.org/10.1158/1538-7445.am2014-1213.

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Vacas-Oleas, A., J. de la Rosa, R. Garcia-Lopez, B. Vera-Cano, G. Gallo-Oller, M. Alfaro, M. H. Shahi i in. "Abstract 257:In vitrotumorigenicity and stemness characterization of the U87MG glioblastoma cell line: Monolayer cultures, neurospheres, and CD133+ and CD133- sorted fractions." W Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1538-7445.am2013-257.

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Cheng, Jierong, Wei Xiong, Shue Ching Chia, Joo Hwee Lim, Shvetha Sankaran i Sohail Ahmed. "Neurosphere segmentation in brightfield images". W SPIE Medical Imaging, redaktorzy Sebastien Ourselin i Martin A. Styner. SPIE, 2014. http://dx.doi.org/10.1117/12.2043365.

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