Academic literature on the topic 'Culture cellulaire en 3 dimensions'
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Journal articles on the topic "Culture cellulaire en 3 dimensions"
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Jubelin, Camille, Javier Munoz-Garcia, Denis Cochonneau, Emilie Moranton, Marie-Françoise Heymann, and Dominique Heymann. "Caractérisation de la dormance d’une lignée cellulaire d’ostéosarcome en culture trois-dimensions." Morphologie 106, no. 354 (September 2022): S25—S26. http://dx.doi.org/10.1016/j.morpho.2022.06.025.
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McGhee, Eric, Juan Uruena, Padraic Levings, Kylie van Meter, Ryan Smolchek, Derek Hood, Catherine Flores, Duane Mitchell, and W. Gregory Sawyer. "TMOD-07. IN SITU MICROSCOPY OF DRUG AND IMMUNE CELL INTERACTIONS AGAINST BIOFABRICATED TUMOR MODELS." Neuro-Oncology 21, Supplement_6 (November 2019): vi263—vi264. http://dx.doi.org/10.1093/neuonc/noz175.1106.
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Abstract BACKGROUND & SIGNIFICANCE Cancer is a disease in 3-dimensions and there is a desperate need for infrastructure and models to study immuno-oncology treatment strategies in 3D. A new culture system for long-duration maturation of patient derived microtumors has been developed. This system enables in situconfocal imaging and movies of T-cells and tumor model interactions, including measurements of T-cell migration, infiltration, and killing. HYPOTHESIS: Biofabrication of 3D microtumors using bioprinting in transparent soft granular gel media can facilitate the precise arrangement and stability of extra-cellular matrix components, tumor, and immune cells while maintaining continuous liquid perfusion. METHODS The design, development, and validation of a modular negative pressure perfusion system controls the transport of liquid growth medium, drugs, antibodies, growth factors, and metabolic waste management in 3D. In situ confocal fluorescent microscopy measures cell positions, velocities, and viability during experiments. Steady perfusion velocities are controlled through negative pressure, and velocities from 1–100 nm/s can be achieved. RESULTS Cell motility, adhesion, and dynamic rearrangement of fibroblasts and endothelial cells within a 3D co-culture of microtumors evolved dramatically over the first 72 hours. Tracking of activated CD8+ T-cells revealed super-diffusive motion in the presence of 3D tumors with a range of 250 µm. Activated T-cell migration speeds have been measured to be between 1.3–2.0 um/min in the 3D media, and preliminary estimates of T cell migration forces are on the order of 1 nN. Arrival of CD8+ T-cells to the tumors within the first 30 minutes revealed cell killing which continued for over 3-hours and resulted in a 2-fold reduction in tumor cell numbers. CONCLUSIONS This integrated system of 3D bioprinting, perfusion culture plates, and confocal microscopy enables in situ3D studies of cancer biology, immunotherapy, and drug treatment regimens and provides unique insights and measurements of immune cell invasion dynamics in 3D microtumors.
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Green, Matthew P., and Bo Hou. "Cellular Changes of Stem Cells in 3-Dimensional Culture." Journal of Oral and Maxillofacial Surgery 75, no. 11 (November 2017): 2477.e1–2477.e9. http://dx.doi.org/10.1016/j.joms.2017.06.007.
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Dey, Nandini, Yuliang Sun, Amy K. Krie, Luis Rojas, David Starks, Xiaoqian Lin, Kirstin Anne Williams, et al. "Three dimensional organotypic ex vivo culture of tissues from post-operated tumor samples: Strengths and limitations." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): e23151-e23151. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e23151.
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e23151 Background: Evolution of tumor occurs in two phases, pretreatment phase, and posttreatment phase.Tumorigenic history and path of tumorigenic evolution determine the response of tumor cells to antitumor drug and thus the outcome of treatment. Carcinomas from the same organ-site with similar genomic alterations in different patients may vary in their tumorigenic history and their diverse paths of tumorigenic evolution which cause them respond differently to the same antitumor drugs. Uniqueness of tumorigenic history and paths of tumorigenic evolution in individual patient makes it ideal to test drugs, N-of-1. Here we present our experience with 3D organotypic ex vivo culture of tumor tissue from post-operated tumor samples. Methods: Informed consent was obtained from patients ( NCT02470715). The investigation was approved by IRB of the Avera Cancer Institute and the Western IRB. Surgically resected tissue was obtained from patients with different tumors of different organ sites including ovarian, breast, lung, endometrium, and cervix at the Avera Cancer Institute, SF, SD. Tissues from patients were collected in two formats, paired samples (tumor and tumor-adjacent normal) and unpaired samples. Results: As extracellular matrix lost in cell cultures, provide important signals for cell survival, differentiation and drug resistance we have established a protocol to culture slices in the 3D format. We have established 3D slice cultures (3x3 mm) of tumor-derived tissues which can be maintained ex vivo for at least three days. Tumor cells / normal cells from different tumors/tumor-adjacent normal tissues from day zero (non-cultured) were used to compare day1, day2, and day3 cultures. At the end of the culture period, slices were embedded in paraffin for histological analysis following H&E staining as well as IHC-staining for proliferation index (Ki-67), cellular proliferation signals (pS6RP), apoptosis (activated caspase 3), or tumor angiogenesis (CD31). Ki67 staining was characteristically different in cultured normal and cultured tumor tissues. Conclusions: Here, we show that tumor-derived tissues survive in 3D Matrigel culture for a minimum of 6 hours and maximum up to 3 days. Clinical trial information: NCT02470715.
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Suderman, Michael T., Kevin B. Temeyer, Kristie G. Schlechte, and Adalberto A. Pérez de León. "Three-Dimensional Culture of Rhipicephalus (Boophilus) microplus BmVIII-SCC Cells on Multiple Synthetic Scaffold Systems and in Rotating Bioreactors." Insects 12, no. 8 (August 19, 2021): 747. http://dx.doi.org/10.3390/insects12080747.
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Tick cell culture facilitates research on the biology of ticks and their role as vectors of pathogens that affect humans, domestic animals, and wildlife. Because two-dimensional cell culture doesn’t promote the development of multicellular tissue-like composites, we hypothesized that culturing tick cells in a three-dimensional (3-D) configuration would form spheroids or tissue-like organoids. In this study, the cell line BmVIII-SCC obtained from the cattle fever tick, Rhipicephalus (Boophilus) microplus (Canestrini, 1888), was cultured in different synthetic scaffold systems. Growth of the tick cells on macrogelatinous beads in rotating continuous culture system bioreactors enabled cellular attachment, organization, and development into spheroid-like aggregates, with evidence of tight cellular junctions between adjacent cells and secretion of an extracellular matrix. At least three cell morphologies were identified within the aggregates: fibroblast-like cells, small endothelial-like cells, and larger cells exhibiting multiple cytoplasmic endosomes and granular vesicles. These observations suggest that BmVIII-SCC cells adapted to 3-D culture retain pluripotency. Additional studies involving genomic analyses are needed to determine if BmVIII-SCC cells in 3-D culture mimic tick organs. Applications of 3-D culture to cattle fever tick research are discussed.
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Clayton, Natasha P., Alanna Burwell, Heather Jensen, Barbara F. Williams, Quashana D. Brown, Pamela Ovwigho, Sreenivasa Ramaiahgari, Tonia Hermon, and Darlene Dixon. "Preparation of Three-dimensional (3-D) Human Liver (HepaRG) Cultures for Histochemical and Immunohistochemical Staining and Light Microscopic Evaluation." Toxicologic Pathology 46, no. 6 (August 2018): 653–59. http://dx.doi.org/10.1177/0192623318789069.
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The use of three-dimensional (3-D) in vitro culture systems (spheroids, organoids) in biomolecular and drug discovery research has become increasingly popular. The popularity is due, in part, to a diminished reliance on animal bioassays and a desire to develop physiologically relevant cell culture systems that simulate the in vivo tissue microenvironment. Most evaluations of 3-D cultures are by confocal microscopy and high-content imaging; however, these technologies do not allow for detailed cellular morphologic assessments or permit basic hematoxylin and eosin histologic evaluations. There are few studies that have reported detailed processes for preparing 3-D cultures for paraffin embedding and subsequent use for histochemical or immunohistochemical staining. In an attempt to do so, we have developed a protocol to paraffin-embed human liver spheroids that can be sectioned with a microtome and mounted onto glass slides for routine histochemical and immunohistochemical staining and light microscopic evaluations.
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Mortera-Blanco, Teresa, Athanasios Mantalaris, Alexander Bismarck, and Nicki Panoskaltsis. "Long-Term in Vitro Cytokine-Free and Serum-Free Culture of Human Cord Blood Mononuclear Cells in a Three-Dimensional Scaffold." Blood 114, no. 22 (November 20, 2009): 503. http://dx.doi.org/10.1182/blood.v114.22.503.503.
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Abstract Abstract 503 The ability to expand cord blood (CB) cells ex vivo overcomes an important limitation to its wider clinical application in cellular therapies. The current practice of hematopoietic cell culture is based on two-dimensional (2D) tissue culture flasks or well plates which require either co-culture with allogeneic or xenogeneic stromal cells and the exogenous provision of several cytokines. This 2D culture environment is artificial and lacks the 3D cellular niches that characterise the in vivo hematopoietic inductive microenvironment. Specifically, the cultured cells are exposed to abnormally high cytokine concentrations, which may result in differentiation and loss of pluripotency. We have previously developed a 3D bone marrow biomimicry through the use of synthetic scaffolds made of poly (D,L-lactide-co-glycolide) (PLGA) and polyurethane (PU) coated with collagen type I. Our previous work has shown that these scaffolds, which were seeded with cord blood (CB) mononuclear cells (MNCs) at a cell density of 3-6×106cells per scaffold (5×5×5mm3), could successfully support long-term culture in the absence of exogenous growth factors for over 4 weeks. Specifically, the 3D biomimicry facilitated a 53-fold total MNC expansion, with an increase in the BFU-E and CFU-GM progenitor cell population. However, these cultures, although cytokine-free, contained 20-30% (v/v) fetal calf serum which can have both conducive and inhibitory effects on hematopoietic cell cultures due to the unknown composition and concentration of humoral factors contained within. Inclusion of serum in expansion-type cultures can limit the clinical application of the derived product. The serum-free and cytokine-free culture and expansion of hematopoietic cells has not been achieved until now. Herein, we report that for at least 4 weeks the polyurethane (PU) scaffolds coated with collagen type I were able to maintain and expand human CB MNCs. Furthermore the progenitor population, as determined by the colony forming unit assay, was also maintained and preferentially directed towards the granulocytic lineage, even though the CFU-GEMMs declined. Immunophenotypic analysis of the extracted cells confirmed the presence of erythroid precursors (CD71+CD45-) as well as early maturing myeloid cells. In contrast, the 2D cytokine- and serum-free cultures collapsed within 3-4 days. We hypothesized that the 3D biomimicry was able to facilitate serum- and cytokine-free conditions because it can recapitulate the three-dimensional architecture of the human bone marrow. This hypothesis was supported by scanning electron microscopy of the central sections of the scaffolds that showed the migration of cells within the pores and establishment of “niche-like” structures. In conclusion, this novel 3D culture system is capable of long-term, cytokine- and serum-free expansion of haematopoietic cells from cord blood, enabling the study of haematopoiesis as well as facilitating the expansion of cells for future clinical applications. Disclosures: No relevant conflicts of interest to declare.
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Baudino, Troy A., Alex McFadden, Charity Fix, Joshua Hastings, Robert Price, and Thomas K. Borg. "Cell Patterning: Interaction of Cardiac Myocytes and Fibroblasts in Three-Dimensional Culture." Microscopy and Microanalysis 14, no. 2 (March 3, 2008): 117–25. http://dx.doi.org/10.1017/s1431927608080021.
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Patterning of cells is critical to the formation and function of the normal organ, and it appears to be dependent upon internal and external signals. Additionally, the formation of most tissues requires the interaction of several cell types. Indeed, both extracellular matrix (ECM) components and cellular components are necessary for three-dimensional (3-D) tissue formationin vitro. Using 3-D cultures we demonstrate that ECM arranged in an aligned fashion is necessary for the rod-shaped phenotype of the myocyte, and once this pattern is established, the myocytes were responsible for the alignment of any subsequent cell layers. This is analogous to thein vivopattern that is observed, where there appears to be minimal ECM signaling, rather formation of multicellular patterns is dependent upon cell–cell interactions. Our 3-D culture of myocytes and fibroblasts is significant in that it modelsin vivoorganization of cardiac tissue and can be used to investigate interactions between fibroblasts and myocytes. Furthermore, we used rotational cultures to examine cellular interactions. Using these systems, we demonstrate that specific connexins and cadherins are critical for cell–cell interactions. The data presented here document the feasibility of using these systems to investigate cellular interactions during normal growth and injury.
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Furubayashi, Tomoyuki, Daisuke Inoue, Noriko Nishiyama, Akiko Tanaka, Reiko Yutani, Shunsuke Kimura, Hidemasa Katsumi, Akira Yamamoto, and Toshiyasu Sakane. "Comparison of Various Cell Lines and Three-Dimensional Mucociliary Tissue Model Systems to Estimate Drug Permeability Using an In Vitro Transport Study to Predict Nasal Drug Absorption in Rats." Pharmaceutics 12, no. 1 (January 17, 2020): 79. http://dx.doi.org/10.3390/pharmaceutics12010079.
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Recently, various types of cultured cells have been used to research the mechanisms of transport and metabolism of drugs. Although many studies using cultured cell systems have been published, a comparison of different cultured cell systems has never been reported. In this study, Caco-2, Calu-3, Madin–Darby canine kidney (MDCK), EpiAirway and MucilAir were used as popular in vitro cell culture systems, and the permeability of model compounds across these cell systems was evaluated to compare barrier characteristics and to clarify their usefulness as an estimation system for nasal drug absorption in rats. MDCK unexpectedly showed the best correlation (r = 0.949) with the fractional absorption (Fn) in rats. Secondly, a high correlation was observed in Calu-3 (r = 0.898). Also, Caco-2 (r = 0.787) and MucilAir (r = 0.750) showed a relatively good correlation with Fn. The correlation between Fn and permeability to EpiAirway was the poorest (r = 0.550). Because EpiAirway forms leakier tight junctions than other cell culture systems, the paracellular permeability was likely overestimated with this system. On the other hand, because MDCK formed such tight cellular junctions that compounds of paracellular model were less likely permeated, the paracellular permeability could be underestimated. Calu-3, Caco-2 and MucilAir form suitable cellular junctions and barriers, indicating that those cell systems enable the precise estimation of nasal drug absorption.
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Poll, B., P. Buttler, H. G. GräBer, F. Lampert, and C. Becker. "Engrafting Periodontal Fibroblasts with New 3-Dimensional Polylactide Foams." International Journal of Artificial Organs 28, no. 8 (August 2005): 827–33. http://dx.doi.org/10.1177/039139880502800808.
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In clinical periodontics, “tissue engineering” techniques have been developed to guide the regenerative process following periodontal disease. We explored a new shaped biomaterial in order to promote cellular adhesion, proliferation and migration of periodontal cells. Granules of poly-D,L-lactide were foamed in specially designed moulds by a controlled gas-loading process. Explant cultures of periodontal tissue were seeded at different densities on the 3-dimensional scaffolds following analysis of cytotoxicity, cell proliferation and differentiation. The moulding procedure led to porous structures with predetermined tubes for cellular locomotion. Cells adhered to and populated the material's surface and inner cavities while retaining fibroblastic phenotype. An optimal ratio between cellular proliferation and mortality rate was achieved at a seeding density of > 106 cells/cm3 scaffold. We designed modified polylactide scaffolds capable of acting as a stent and a cell carrier matrix. The foaming process is easy, cheap and suitable for commercial production.
Dissertations / Theses on the topic "Culture cellulaire en 3 dimensions"
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De, Conto Véronique. "Importance du microenvironnement dans les modèles cérébraux in vitro pour le criblage phénotypique." Thesis, Université de Lille (2018-2021), 2021. http://www.theses.fr/2021LILUS046.
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Environ 90% des candidats-médicaments échouent en phase clinique, pour des raisons d’efficacité ou de toxicité qui impliquent souvent le système nerveux central (SNC). Ce fort taux d’échec souligne un manque de pertinence des modèles expérimentaux utilisés en amont, dont les modèles in vitro de cellules humaines. En effet, ces derniers ne prennent pas en compte toute la complexité du SNC, où les neurones organisés en 3 dimensions (3D) interagissent avec leur microenvironnement composé de cellules, de facteurs solubles et des molécules de la matrice extracellulaire (MEC). Les objectifs de ce travail étaient i) d’étudier l’influence de ces trois composantes du microenvironnement sur les cellules neuronales dans des modèles cérébraux in vitro par imagerie cellulaire automatisée, et ii) de développer des modèles cérébraux in vitro plus pertinents pour évaluer les effets neurotoxiques ou thérapeutiques de molécules par criblage phénotypique, notamment dans le cadre de la maladie de Parkinson (MP).Dans un premier temps, la technologie BIOMIMESYS® Brain a été développée. Cette matrice à base d’acide hyaluronique permet de mimer la MEC et de cultiver des cellules cérébrales en 3D dans des plaques 96 puits. La sensibilité des cellules Luhmes, une lignée de neurones dopaminergiques, aux inducteurs de la MP a été étudiée : les cellules ont montré une sensibilité plus faible dans BIOMIMESYS® Brain qu’en 2 dimensions (2D). Cette différence a pu être expliquée par deux phénomènes : une rétention partielle des molécules toxiques dans la matrice, et un phénotype de neurone dopaminergique moins mature qu’en 2D. L’importance du microenvironnement cellulaire a ensuite été étudiée au travers d’une co-culture de cellules Luhmes et d’astrocytes primaires humains en 2D. Cette co-culture a ensuite été transposée dans la matrice BIOMIMESYS®, formant ainsi un modèle complexe incluant à la fois le microenvironnement glial et le microenvironnement matriciel.En parallèle, l’influence du microenvironnement moléculaire a été étudiée sur les cellules SH-SY5Y, une lignée cellulaire issue d’un neuroblastome, couramment utilisée pour évaluer la neurotoxicité de molécules. Dans cette étude, les 24 principaux milieux décrits dans la littérature pour différencier ces cellules en neurones ont été criblés. Les 3 conditions les plus différenciantes en matière de ralentissement de la prolifération cellulaire et de croissance des neurites ont été sélectionnées : l’acide rétinoïque, la staurosporine, et l’Adénosine Monophosphate cyclique (AMPc) associée à du supplément B21. L’expression de marqueurs protéiques neuronaux et la sensibilité des cellules à des composés de toxicités connues ont été mesurées, en 2D et en 3D dans BIOMIMESYS® Brain. La maturité neuronale et la sensibilité aux composés neurotoxiques différaient selon le milieu, en étant les plus hautes en milieu B21+AMPc. La culture en 3D modifiait aussi la réponse des cellules, avec une sensibilité plus faible comparée aux cellules cultivées en 2D.Cette thèse a mis en évidence que le microenvironnement des neurones, qui inclut la MEC, les cellules gliales et les facteurs solubles, modifie la réponse neuronale in vitro et devrait par conséquent être considéré avec attention dans la recherche académique comme industrielle, dès les étapes de criblage de nouveaux médicamentsAbout 90% of drug candidates fail in clinical trials, for efficacy- and toxicity-related reasons, which often involve the Central Nervous System (CNS). This high failure rate highlights a lack of relevance in experimental models used upstream, including human in vitro models. Indeed, they do not take into account the complexity of the CNS, in which neurons are organized in 3 dimensions (3D) and interact with their microenvironment, composed of cells, soluble factors and extracellular matrix (ECM). The objectives of this PhD were i) to study the influence of these three microenvironment components on neuronal cells in cerebral in vitro models by automatized cellular imaging, and ii) to develop more relevant cerebral in vitro models for phenotypic screening, to assess neurotoxic or therapeutic effects, in the frame of Parkinson’s Disease (PD).First, the BIOMIMESYS® Brain technology has been developed. This acid hyaluronic based-matrix allows the simulation of the ECM and a 3D culture of cerebral cells in 96-well plates. The sensitivity of Luhmes cells, a dopaminergic neuronal cell line, to PD inducers has been studied: the cells displayed a lower sensitivity in BIOMIMESYS® Brain compared to cells cultured in 2 dimensions (2D). This difference was explained by two phenomena: a partial retention of toxic molecules in the matrix, and a lower neuronal maturity compared to cells cultured in 2D.The importance of the cellular microenvironment has been studied through a co-culture of Luhmes cells and primary human astrocytes in 2D. This co-culture has then been transposed in BIOMIMESYS® matrix, to form a complex model including both the glial and the matricial microenvironments.In parallel, the influence of the molecular microenvironment has been studied on the SH-SY5Y cells, a cell line derived from a neuroblastoma, commonly used for neurotoxicity assessment. In this study, the 24 major differentiation media described in the literature to differentiate these cells into neurons have been screened. The 3 most differentiating conditions in terms of proliferation slowdown and neurite elongation have been selected: retinoic acid, staurosporine, and cyclic Adenosine Monophosphate (cAMP) combined to B21 supplement. The neuronal protein marker expression and the cell sensitivity to compounds of known-toxicity have been measured, in 2D and in 3D in BIOMIMESYS® Brain. Both maturity and sensitivity of these neurons varied according to the differentiation medium, and were higher in B21+cAMP. The 3D cell culture modified also the cell response, with a lower sensitivity of cells cultured in 2D.This PhD highlighted that the microenvironment of neurons, including the ECM, the glial cells and the soluble factors, can modify the neuronal response in vitro, and should thus be considered carefully in academic research and as early as possible in the drug discovery industrial process
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Desmaison, Annaïck. "Impact des contraintes mécaniques sur la division cellulaire : analyse dans modèle tumoral multicellulaire en 3 dimensions : le sphéroïde." Toulouse 3, 2014. http://thesesups.ups-tlse.fr/2367/.
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Une tumeur est une structure hautement organisée en 3D, intégrant des relations entre les cellules et avec son environnement. Le remodelage de l'environnement par la tumeur et sa croissance dans un environnement restreint induisent un déséquilibre de l'homéostasie tissulaire et l'accumulation d'un stress mécanique au niveau de la tumeur. Il a été montré que ce stress mécanique est un paramètre important du développement tumoral qui influence, entre autre, la migration et la prolifération des cellules tumorales. Un des aspects majeurs du contrôle de la prolifération cellulaire est la régulation du cycle cellulaire. De nombreuses études montrent que le déroulement de la mitose, étape de division du cycle cellulaire, est régulée par les propriétés mécaniques de l'environnement cellulaire. Cependant, l'impact des contraintes mécaniques sur la progression en mitose a essentiellement été étudié sur des modèles de culture en monocouche et les conséquences induites sur le développement tumoral sont encore méconnues. Dans ce contexte, l'objectif de mes travaux est d'étudier l'impact des contraintes mécaniques sur la division cellulaire, dans un modèle tumoral multicellulaire 3D, le sphéroïde. Ce modèle mime l'organisation multicellulaire et l'hétérogénéité cellulaire telles qu'elles existent in vivo dans des microrégions tumorales. Afin de mimer un environnement confiné, des microsdispositifs ont été fabriqués pour restreindre la croissance et contraindre mécaniquement les sphéroïdes. Ces conditions expérimentales nous ont permis de démontrer que la contrainte mécanique altère la division des cellules au sein des sphéroïdes. L'étude de la dynamique de progression en mitose de sphéroïdes contraints dans un dispositif en agarose adapté à l'imagerie en temps réel, a révélé un délai en prométaphase induit par la contrainte mécanique, probablement du à un défaut transitoire de mise en place du fuseau bipolaire et impliquant le cytosquelette d'actomyosine. Ce défaut ne semble pas induire un défaut d'orientation préférentiel de l'axe de division observé dans les sphéroïdes. De plus, ces résultats montrent qu'en condition de croissance en présence d'un stress mécanique, des traitements déstabilisant le cytosquelette d'actomyosine n'induisent pas d'altération de la mitose, suggérant que des voies de signalisation permettant d'éviter les erreurs de progression en mitose soient activées. L'ensemble de ces résultats suggèrent que la contrainte mécanique induite par la croissance progressive des sphéroïdes dans un environnement confiné ralentit la progression en mitose. Ce ralentissement peut être responsable d'erreurs de ségrégations des chromosomes induisant une augmentation de l'instabilité génétique et une hétérogénéité cellulaire. Cette hétérogénéité est caractéristique des tumeurs et souvent responsable de l'efficacité limitée des stratégies thérapeutiques actuelles. Les travaux réalisés viennent enrichir les connaissances de la réponse des cellules tumorales à leur environnement mécanique tel qu'il existe in vivo et ses conséquences sur le développement tumoral. Il permet aussi d'identifier les caractéristiques importantes des paramètres mécaniques à prendre en compte pour définir l'efficacité des traitements, et ouvre de nouvelles perspectives de thérapies antitumoralesA tumor micro-region consists of a heterogeneous cancer cell population organized in a 3D structure in which cell growth is influenced by interaction with the microenvironment. Changes in mechanical homeostasis within tissues are observed during tumor growth, leading to high pressure and tension forces within the growing tumor. Those changes in mechanical properties of the microenvironment participate to tumor development by influencing, amongst others, proliferation and migration of tumor cells. One important aspect of the control of proliferation is the regulation of the cell cycle. Many studies have demonstrated that mitosis progression, the division process of cell cycle, is not only biochemically regulated, but also mechanically regulated. However, the impact of mechanical cues on mitotic progression has essentially been documented using 2D monolayer-based models and very little is known about the consequences of mechanical stress on cell division within tumors. In this context, my goal was to investigate the impact of mechanical stress on cell division in MultiCellular Tumor Spheroids (MCTS), an in vitro model that mimics 3D cell organization and heterogeneity found in tumor microregions in vivo. We first induced mechanical stress on MCTS by restricting their growth in a confined environment. We demonstrated that mechanical stress impairs cell division. The study of the dynamics of mitosis progression within MCTS mechanically constrained in agarose, showed that mechanical stress induces a delay in prometaphase. This delay may be due to a transient defect in spindle assembly, and possibly implies actin filament dynamics. This defect in spindle assembly does not seem to induce a preferential orientation deviation of the division axis of cells within spheroids. Futhermore, we showed that in this mechanical stressed condition, drugs destabilizing the actomyosin cytoskeleton do not alter mitosis anymore, suggesting that signaling pathways could be activated and avoid aberrant mitosis progression. Altogether these results suggest that mechanical stress induced by progressive confinement of growing spheroid could slow down mitotic progression. However, a defect in mitosis progression could lead to chromosomes missegregation, responsible for increased genomic instability and cellular heterogeneity. This genetic heterogeneity characteristic of tumors is one of the major reasons for the limited efficiency of current therapeutic strategies. Mechanical stress might also induce the activation of specific pathways able to bypass the effect of certain drugs. This study paves the way for future research to a better understanding of the tumor cell response to mechanical cues similar to those encountered during in vivo tumor development. It could contribute to defining important characteristics of mechanical parameters of tumor on drug efficiency and open new perspectives in anti-tumor therapy
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BOUHOUCHE, NAIMA. "Glucosylation de la 3-demethylthiocolchicine par une suspension cellulaire de centella asiatica : caracterisation et purification de la glycosyltransferase (doctorat : structure et fonctionnement des systemes biologiques integres)." Paris 11, 1998. http://www.theses.fr/1998PA114819.
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Cullen, Daniel Kacy. "Traumatically-Induced Degeneration and Reactive Astrogliosis in 3-D Neural Co-Cultures: Factors Influencing Neural Stem Cell Survival and Integration." Diss., Georgia Institute of Technology, 2005. http://hdl.handle.net/1853/7584.
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Traumatic brain injury (TBI) results from a physical insult to the head and often results in temporary or permanent brain dysfunction. However, the cellular pathology remains poorly understood and there are currently no clinically effective treatments. The overall goal of this work was to develop and characterize a novel three-dimensional (3-D) in vitro paradigm of neural trauma integrating a robust 3-D neural co-culture system and a well-defined biomechanical input representative of clinical TBI. Specifically, a novel 3-D neuronal-astrocytic co-culture system was characterized, establishing parameters resulting in the growth and vitality of mature 3-D networks, potentially providing enhanced physiological relevance and providing an experimental platform for the mechanistic study of neurobiological phenomena. Furthermore, an electromechanical device was developed that is capable of subjecting 3-D cell-containing matrices to a defined mechanical insult, with a predicted strain manifestation at the cellular level. Following independent development and validation, these novel 3-D neural cell and mechanical trauma paradigms were used in combination to develop a mechanically-induced model of neural degeneration and reactive astrogliosis. This in vitro surrogate model of neural degeneration and reactive astrogliosis was then exploited to assess factors influencing neural stem cell (NSC) survival and integration upon delivery to this environment, revealing that specific factors in an injured environment were detrimental to NSC survival. This work has developed enabling technologies for the in vitro study of neurobiological phenomena and responses to injury, and may aid in elucidating the complex biochemical cascades that occur after a traumatic insult. Furthermore, the novel paradigm developed here may provide a powerful experimental framework for improving treatment strategies following neural trauma, and therefore serve as a valid pre-animal test-bed.
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Moura, Campos Doris. "Cultivo de células osteoprogenitoras em compósito 3-D hidroxiapatita-colágeno sob condições estática e dinâmica." Phd thesis, Université de Haute Alsace - Mulhouse, 2012. http://tel.archives-ouvertes.fr/tel-00725990.
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L'organisme humain présente de nombreuses constantes de régénération tissulaires et c'est cette caractéristique essentielle qui maintient l'équilibre physiologique. Toutefois, l'existence de lésions importantes provoquée par un déséquilibre interne ou externe peut empêcher l'organisme de s'auto-régénerer. Dans ce cas, l'application des biomatériaux développés pour des applications biomédicales peuvent améliorer le processus de guérison. Pour les applications en tissus durs, les biomatériaux doivent posséder des propriétés similaires aux matrices naturelles tant sur le plan biologique que physico-mécanique. Dans les applications en bioingénierie osseuse, les composites à base de collagène (Col) et d'hydroxiapatite (HA) sont devenus tellement performant qu'ils peuvent être classifiés comme des matériaux biomimétiques. Cette thèse propose la production d'une matrice 3-D poreuse à base d'HA et de Col (50:50wt%). Ce composite réticulé par le glutaraldéhyde a été caractérisé par des différentes techniques et servira de support pour la culture cellulaire. Des cellules estromales ostéoprogénitrices ont été cultivées dans un environnement statique et dynamique (deux vitesse de flux) et leurs capacités de colonisation ainsi que leurs comportements d'adhésion, de prolifération, de différentiation seront observés. A travers les résultats de diffraction de rayons X et de spectroscopie infrarouge, il est possible d'affirmer la présence dans la matrice collagène d'une phase minérale peu cristalline constituée par de l'hydroxiapatite carbonatée du type-B déficiente en calcium. La viabilité cellulaire a été fortement influencée par les systèmes de culture au cours des 21 jours. Les résultats du système dynamique en haute vitesse montrent une excellente capacité du composite à supporter les processus cellulaires. Les cellules sont capables d'adhérer, de proliférer et de coloniser la matrice tridimensionnelle.
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Esfandiari, Ali-Asghar. "Regulation de la desiodase de type 3 dans les cultures d'astrocytes par l'acide retinoique et la 3,5,3'-triiodothyronine et mise en evidence de la sulfatation des produits de desiodation." Paris 11, 1994. http://www.theses.fr/1994PA11T016.
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Arock, Michel. "Etudes sur la différenciation et la régulation des mastocytes." Paris 5, 1988. http://www.theses.fr/1988PA05P504.
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Bellingard, Valérie. "Etude in vitro des relations paracrines entre le stroma de l'endomètre et les cytotrophoblastes : inhibition de la sécrétion endométriale de la prométalloprotéinase-3." Montpellier 1, 1996. http://www.theses.fr/1996MON1T011.
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Dubois, Clémence. "Optimisation du traitement du cancer du sein Triple-Négatif : développement des modèles de culture cellulaire en trois dimensions, efficacité de l'Olaparib (anti-PARP1) en combinaison avec la radiothérapie et chimiorésistance instaurée par les protéines Multi Drug Résistance." Thesis, Université Clermont Auvergne (2017-2020), 2018. http://www.theses.fr/2018CLFAS018/document.
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Le cancer du sein est une maladie complexe et difficile à caractériser. Parmi les différents sous-types moléculaires, les tumeurs du sein Triple-Négatives (TN) sont particulièrement agressives et de mauvais pronostic. Elles sont caractérisées par une absence d’expression des récepteurs aux œstrogènes (ER), à la progestérone (PR), l’absence de surexpression du récepteur Human Epidermal growth factor 2 (HER2) et de fréquentes mutations sur les gènes BRCA1/2 (profil « BRCAness »). En absence de thérapies ciblées efficaces, de nombreux traitements ciblés notamment les inhibiteurs de poly-ADP-ribose polymérases (anti-PARPs) sont actuellement en cours de développement, en recherche préclinique et clinique. Basés sur le principe de létalité synthétique, les anti-PARPs ciblent les propriétés BRCAness des tumeurs TN. Dans ce contexte, ces travaux de recherche ont été orientés sur le développement d’outils diagnostics afin d’optimiser l’efficacité des anti-PARPs sur des tumeurs TN. Pour ce faire, dans un premier temps, des cultures cellulaires en 3D via la technique Liquid Overlay ainsi que des tests de cytotoxicités associés ont été développés, à partir des lignées cellulaires MDA-MB-231 et SUM1315 de phénotype TN. Ces deux modèles de sphéroïdes ont ensuite été optimisés/normalisés dans un milieu de culture synthétique intitulé OPTIPASS (BIOPASS). Dans un deuxième temps, l’efficacité d’un co-traitement combinant l’anti-PARP1 Olaparib à faibles et à fortes doses et la radiothérapie fractionnée (5x2 Gy) a été modélisée sur les deux lignées MDA-MB-231 et SUM1315, en conditions 2D et 3D. Ces expériences ont clairement mis en évidence un effet potentialisateur de l’Olaparib sur la radiothérapie (i) en présence de faibles doses de cet anti-PARP (5 µM ou inférieur) (ii) à long terme et (iii) en présence d’un fractionnement maximum (5x2 Gy). De plus, les lignées tumorales TN étudiées présentaient des différences de sensibilité vis-à-vis du co-traitement. Ainsi, une analyse transcriptomique in silico a mis en évidence des profils très différents de ces lignées hautement métastatiques et très agressives. Notamment, la lignée SUM1315 semblait présenter un engagement neuronal, suggérant son origine métastatique cérébrale. Ces résultats encourageants pourraient ouvrir de nouvelles perspectives pour le traitement des métastases cérébrales de tumeurs mammaires TN, très fréquentes chez ce sous-type. Dans un troisième temps, afin de mieux caractériser le mode d’action de l’Olaparib sur ces modèles de sphéroïdes, un dérivé fluorescent de l’Olaparib, l’Ola-FL, a été synthétisé et caractérisé. L’analyse de la pénétration et de la distribution de l’Ola-FL au sein des sphéroïdes MDA-MB-231 et SUM1315 a mis en évidence une distribution rapide et homogène du composé ainsi que sa persistance après 3h d’incubation, dans toute la profondeur des sphéroïdes et notamment dans les zones hypoxiques centrales. Enfin, l’analyse de la co-expression de deux pompes Multidrug Resistance (MDR) majeures, la MRP7 et la P-gp après le traitement des deux lignées TN avec l’Olaparib, a mis en évidence sur les cultures 2D, une expression de type relai de la MRP7 et la P-gp. Sur les sphéroïdes traités avec une faible dose d’Olaparib à long terme, une expression basale de la MRP7 et une surexpression de la P-gp ont été détectées, au sein des cellules résiduelles périphériques des sphéroïdes. Ces résultats mettent clairement en évidence l’implication des pompes d’efflux dans les mécanismes de résistances à l’Olaparib, dans ces tumeurs agressives. L’ensemble des résultats issus de la modélisation de l’action de l’Olaparib sur des sphéroïdes MDA-MB-231 et SUM1315 laissent supposer sa plus grande efficacité à faible dose et à long-terme, notamment dans les zones hypoxiques des sphéroïdes, probablement aussi à l’origine de son effet potentialisateur avec la radiothérapieBreast cancer is a very complex and heterogeneous disease. Among the different molecular subtypes, Triple-Negative (TN) breast cancers are particularly aggressive and of poor prognosis. TN tumours are characterized by a lack of estrogen receptors expression (ER), progesterone receptors expression (PR), the absence of Human Epidermal growth factor receptor 2 overexpression (HER2) of the frequent mutations on BRCA1 / 2 genes ("BRCAness" phenotype). In the absence of effective targeted therapies, many targeted therapies including poly-ADP-ribose polymerase inhibitors (anti-PARPs) are currently under development in preclinical and clinical studies. Based on the synthetic lethality concept, the anti-PARPs specifically target the BRCAness properties of TN tumors. In this context, these works were focused on the development of diagnostic tools for the optimization of TN tumours treatment with anti-PARPs. For this, firstly, 3D cell cultures formed with the Liquid Overlay technique as well as associated cytotoxicity tests were developed, from the TN breast cancer cell lines MDA-MB-231 and SUM1315. These two spheroid models were then optimized and standardized in a synthetic culture medium called OPTIPASS (BIOPASS). Secondly, the efficacy of a co-treatment combining anti-PARP1 Olaparib at low and high doses and fractioned radiotherapy (5x2 Gy) was analyzed on the two cell lines MDA-MB-231 and SUM1315 cultured in 2D and 3D conditions. These experiments clearly demonstrated a potentiating effect of Olaparib on radiotherapy (i) in presence of low doses of this anti-PARP (5 μM or inferior) (ii) at long term and (iii) in presence of the maximum fractionation (5x2 Gy). In addition, these two TN cell lines showed a heterogeneous sensitivity to the co-treatment. Thus, an in silico transcriptomic analysis revealed very different profiles of these highly metastatic and highly aggressive cell lines. Notably, the SUM1315 cell line presented a neuronal commitment, suggesting its cerebral metastatic origin. These promising results could open up new perspectives for the treatment of TN tumours brain metastases, which are very common in this subtype. Thirdly, in order to better characterize the mode of action of Olaparib on these spheroid models, a fluorescent derivative of Olaparib, Ola-FL, was synthesized and characterized. The analysis of Ola-FL penetration and distribution in MDA-MB-231 and SUM1315 spheroids showed a rapid and homogeneous distribution of the compound as well as its persistence after 3h of incubation, in all the depth of the spheroids and especially in the central hypoxic zones. Finally, the analysis of the co-expression of two major Multidrug Resistance (MDR) pumps, MRP7 and P-gp after the treatment of the two TN lines with Olaparib, revealed on 2D cultures, a relay type expression of the MRP7 and the P-gp. On spheroids treated with a low dose of Olaparib art long term (10 days), a basal expression of MRP7 and an overexpression of P-gp were detected in the peripheral residual cells of the spheroids. These results clearly highlighted the involvement of these efflux pumps in Olaparib resistance mechanisms, in these aggressive tumors. All the results resulting from the modeling of the action of Olaparib on MDA-MB-231 and SUM1315 spheroids suggest its greater efficacy at low dose and at long-term, especially in the hypoxic zones of the spheroids. This parameter might be probably at the origin of its potentiating effect with radiotherapy
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Du, Cheyron Damien. "1. Régulation de l'échangeur Na/H isoforme 3 (NHE) en conditions physiologiques et physiopathologiques : rôle du cytosquelette d'actine - Effet de l'angiotensine II. 2. Identification de NHE3 comme biomarqueur urinaire de l'insuffisance rénale aigue." Paris 6, 2006. http://www.theses.fr/2006PA066105.
Full textBooks on the topic "Culture cellulaire en 3 dimensions"
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Kunert, Sophie. The Eight Universal Dimensions of Culture from a Synthesis of Cultural Taxonomies. Wiesbaden: Springer Fachmedien Wiesbaden, 2022. http://dx.doi.org/10.1007/978-3-658-38765-5.
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Henry, Kevin. May Fourth and Translation. Venice: Fondazione Università Ca’ Foscari, 2020. http://dx.doi.org/10.30687/978-88-6969-465-3.
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The May 4th Movement in 1919 – and more broadly the so-called New Culture movement in the 1910s and 1920s, – a landmark in the history of China, was marked by a great wave of translations, without precedent other than the one inspired by the Buddhist faith more than 1000 years before. This volume, which includes five papers presented at the conference 4 May 1919: History in Motion (Université de Mons, Belgium, 2-4 May 2019), seeks to define and measure, in all its dimensions and complexity (from tragic theatre to revolutionary novels to literary journals), the impact of this intense translation effort in the early years of Republican China.
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Dr. John Rouse, and Dr. David Serlin Dr. Robert Cancel. Dimensions of Culture 3: Imagination (Spring 2010). University Readers, 2010.
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Borges, Damião Conceição de Souza, and Sandra Célia Coelho Gomes Silva. Pensar e construir: Experiência e vivências. Brazil Publishing, 2020. http://dx.doi.org/10.31012/978-65-5861-040-3.
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In the face of a society that liquefies the dimensions of human existence, this project of strengthening institutional links is quite significant, as there is a concern with the formation of the human person as a whole. At the present time, self-donation seems to go against the prevailing “cultural” current. However, this work is proof that the collaborative dimension must be enhanced. Taking advantage of the institutional purpose in the various Campuses of the University of the State of Bahia (UNEB) and the interest of the Diocese of Ilhéus to build partnerships, an intertwining of interests arose, made positive by the conclusion of an agreement, the result of a pilgrimage of knowledge, juxtaposed in a common interest. The current “culture”, marked by immanence, which imprisons the human being in the immediate and does not respond to his deepest aspirations regarding the meaning of life, lacks a humanism that is capable of showing the existence of the Divine. The Ilheus School of Theology (ETEL), which aims to train its lay people, was based on the curricular structure of the Institute of Theology of the Diocese of Ilhéus, which became one of the most renowned institutes of Philosophy and Theology in Brazil. Through this agreement with UNEB, it was possible to academically institutionalize a relevant action already developed by the diocese. This partnership experience between UNEB and ETEL was and has been enriching, with gains for both institutions.
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Terhechte, Jörg Philipp, ed. Rechtsgespräche. Nomos Verlagsgesellschaft mbH & Co. KG, 2022. http://dx.doi.org/10.5771/9783748926054.
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Four guiding themes on (also) legal issues characterise Leuphana University Lüneburg: 1. "Innovation & Entrepreneurship", i.e. the legal and economic dimensions of entrepreneurship and innovation; 2. "Sustainability" as a formative key concept in current social discussions; 3. the tension between "law and culture", which is reflected in the concept of "legal culture"; 4. and finally, the relationship between "Europe and the law", which is evident both in the difficulties and crises that currently characterise the EU, but also in the undeniable successes of the European integration process. The volume documents four interdisciplinary law discussions on these central themes. Andreas Voßkuhle, former President of the Federal Constitutional Court, builds the bridge in his closing statement.
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Strauder-Porchet, Julie, Elizabeth Frood, and Andréas Stauder, eds. Ancient Egyptian Biographies. Lockwood Press, 2020. http://dx.doi.org/10.5913/2020280.
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(Auto-)biography is a genre of ancient Egyptian written discourse that was central to high culture from its earliest periods. Belonging to the nonroyal elites, these texts present aspects of individual lives and experience, sometimes as narratives of key events, sometimes as characterizations of personal qualities. Egyptian (auto-) biographies offer a unique opportunity to examine the ways in which individuals fashioned distinctive selves for display and the significance of the physical, religious, and social contexts they selected. The present volume brings together specialists from a range of relevant periods, approaches, and interests. The studies collected here examine Egyptian (auto-)biographies from a variety of complementary perspectives: (1) anthropological and contrastive perspectives; (2) the original Old Kingdom settings; (3) text format and language; (4) social dimensions; and (5) religious experience.
Book chapters on the topic "Culture cellulaire en 3 dimensions"
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de Mooij, Marieke. "Culture and Cultural Dimensions." In Human and Mediated Communication around the World, 173–204. Cham: Springer International Publishing, 2013. http://dx.doi.org/10.1007/978-3-319-01249-0_6.
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Qi, Zifeng, Haiguang Chen, Mingxing Liu, and JianJiang Wang. "Bie—Modernism with Cultural Calculations in Multiple Dimensions." In Culture and Computing, 120–36. Cham: Springer International Publishing, 2022. http://dx.doi.org/10.1007/978-3-031-05434-1_8.
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Seeler, Jürgen-Matthias, Anja Fuchs, Thomas Stöckl, and Karin Sixl-Daniell. "Whistleblowing and Culture: A Case for CSR in Developing Markets." In International Dimensions of Sustainable Management, 219–29. Cham: Springer International Publishing, 2019. http://dx.doi.org/10.1007/978-3-030-04819-8_13.
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Siliquini-Cinelli, Luca, and Andrew Hutchison. "Comparative Constitutional Contract Law: A Question of Legal Culture." In More Constitutional Dimensions of Contract Law, 1–13. Cham: Springer International Publishing, 2019. http://dx.doi.org/10.1007/978-3-030-15107-2_1.
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Pauluzzo, Rubens, and Bin Shen. "Culture and Its Dimensions: General Implications for Management." In Impact of Culture on Management of Foreign SMEs in China, 91–138. Cham: Springer International Publishing, 2018. http://dx.doi.org/10.1007/978-3-319-77881-5_4.
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Mohamed, Mona A. "The Effects of Culture on Authentication Cognitive Dimensions." In Advances in Intelligent Systems and Computing, 37–42. Cham: Springer International Publishing, 2019. http://dx.doi.org/10.1007/978-3-030-11051-2_6.
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Gould, William T. S. "Knowledge, Behavior, and Culture: HIV/AIDS in Sub-Saharan Africa." In Ethnic and Cultural Dimensions of Knowledge, 275–92. Cham: Springer International Publishing, 2016. http://dx.doi.org/10.1007/978-3-319-21900-4_13.
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Harder, Nicolas L., and Matthew E. Brashears. "A Hybrid Cellular Model for Predicting Organizational Recruitment in a k-Dimensional Space." In Social, Cultural, and Behavioral Modeling, 163–72. Cham: Springer International Publishing, 2019. http://dx.doi.org/10.1007/978-3-030-21741-9_17.
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Dasgupta, Subhasish, and Babita Gupta. "Organization Culture Dimensions as Antecedents of Internet Technology Adoption." In Grand Successes and Failures in IT. Public and Private Sectors, 658–62. Berlin, Heidelberg: Springer Berlin Heidelberg, 2013. http://dx.doi.org/10.1007/978-3-642-38862-0_49.
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Kunert, Sophie. "Questionnaire for the Eight Universal Dimensions of Culture (UDCs)." In The Eight Universal Dimensions of Culture from a Synthesis of Cultural Taxonomies, 233–323. Wiesbaden: Springer Fachmedien Wiesbaden, 2022. http://dx.doi.org/10.1007/978-3-658-38765-5_8.
Full textConference papers on the topic "Culture cellulaire en 3 dimensions"
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Zavrel, Erik A., Michael L. Shuler, and Xiling Shen. "A Simple Aspect Ratio Dependent Method of Patterning Microwells for Selective Cell Attachment." In 2018 Design of Medical Devices Conference. American Society of Mechanical Engineers, 2018. http://dx.doi.org/10.1115/dmd2018-6811.
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3-D culture has been shown to provide cells with a more physiologically authentic environment than traditional 2-D (planar) culture [1, 2]. 3-D cues allow cells to exhibit more realistic functions and behaviors, e.g., adhesion, spreading, migration, metabolic activity, and differentiation. Knowledge of changes in cell morphology, mechanics, and mobility in response to geometrical cues and topological stimuli is important for understanding normal and pathological cell development [3]. Microfabrication provides unique in vitro approaches to recapitulating in vivo conditions due to the ability to precisely control the cellular microenvironment [4, 5]. Microwell arrays have emerged as robust alternatives to traditional 2D cell culture substrates as they are relatively simple and compatible with existing laboratory techniques and instrumentation [6, 7]. In particular, microwells have been adopted as a biomimetic approach to modeling the unique micro-architecture of the epithelial lining of the gastrointestinal (GI) tract [8–10]. The inner (lumen-facing) surface of the intestine has a convoluted topography consisting of finger-like projections (villi) with deep well-like invaginations (crypts) between them. The dimensions of villi and crypts are on the order of hundreds of microns (100–700 μm in height and 50–250 μm in diameter) [11]. While microwells have proven important in the development of physiologically realistic in vitro models of human intestine, existing methods of ensuring their surface is suitable for cell culture are lacking. Sometimes it is desirable to selectively seed cells within microwells and confine or restrict them to the microwells in which they are seeded. Existing methods of patterning microwells for cell attachment either lack selectivity, meaning cells can adhere and migrate anywhere on the microwell array, i.e., inside microwells or outside of them, or necessitate sophisticated techniques such as micro-contact printing, which requires precise alignment and control to selectively pattern the bottoms of microwells for cell attachment [12, 13].
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Lelkes, Peter I., and Brian R. Unsworth. "Cellular Signaling Mechanisms Involved in the 3-Dimensional Assembly and Differentiation of PC12 Pheochromocytoma Cells Under Simulated Microgravity in NASA Rotating Wall Vessel Bioreactors." In ASME 1998 International Mechanical Engineering Congress and Exposition. American Society of Mechanical Engineers, 1998. http://dx.doi.org/10.1115/imece1998-0791.
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Abstract Rotating Wall Vessel (RWV) Bioreactors simulate microgravity and facilitate 3-D tissue-like assembly through spatial co-localization and cell-cell interactions. This unique cell culture venue is well suited to assess the role of micro-environmental cues in the assembly and tissue-specific differentiation of cells in culture. Our long term goal is to use RWV Bioreactors for generating functional neuroendocrine 3-D constructs which may be useful as clinical replacement tissue in treating neurodegenerative diseases. As a model we are using PC12 pheochromocytoma cells, a bipotential rat adrenal medullary tumor cell line. PC 12 cells differentiate, depending on exogenous factors, either along the neuronal or the neuroendocrine pathway. PC12 cells, when maintained for up to 20 days in RWV Bioreactors, form macroscopic tissue-like aggregates which exhibit enhanced expression of neuroendocrine, adrenergic differentiation markers (Lelkes et al., In Vitro Devel. Biol, 1998, 34: 316–325). We hypothesized that exposure of PC12 cells to the “simulated microgravity” culture conditions in the RWV Bioreactors, might selectively activate signal transduction pathways leading to enhanced neuroendocrine adrenergic differentiation. Using quantitative RT-PCR we demonstrated rapid upregulation of an adrenergic marker, phenylethanolamine-N-methyl transferase (PNMT), in short term RWV cultures. Concomitantly, we found, by electrophoretic mobility shift assays, differential induction of nuclear transcription factors, such as GRE and SP-1, which are known to be involved in the glucocorticoid-induced activation of PNMT. Conversely, upon short term culture of PC12 cells in RWV, the neuronal traits of the cells were impaired. Upon exposure to simulated microgravity, MAPK signaling (erk and jnk) was constitutively activated, while nerve-growth factor (NGF)-induced activation of erk, was abrogated. These results suggest that the culture conditions in the RWV Bioreactors are sufficient to induce PC12 cell differentiation towards the neuroendocrine, phenotype by upregulating “adrenergic” gene expression, while downregulating neurotrophin signaling pathways.
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Roby, Tiffany S., and Jiro Nagatomi. "Effect of Stretch on Bladder Smooth Muscle Cells in Three-Dimensional Culture." In ASME 2007 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2007. http://dx.doi.org/10.1115/sbc2007-176611.
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The bladder is routinely subjected to mechanical stretch from filling cycles; however, abnormal bladder distention can result from pathological conditions such as bladder outlet obstruction. It has been suggested that abnormal mechanical environments in the bladder trigger cellular and molecular changes, such as smooth muscle cell hyperplasia or hypertrophy and alteration of the extracellular matrix (ECM). These cellular and ECM changes can, in turn, deteriorate the function of the bladder by decreasing the contractility and compliance of the tissue [1, 3, 5].
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Nicoll, Steven B., Robert L. Mauck, Rick C. Tsay, Clark T. Hung, and Gerard A. Ateshian. "Intermittent Hydrostatic Pressurization Modulates Gene Expression in Human Dermal Fibroblasts Seeded in Three-Dimensional Polymer Scaffolds." In ASME 2002 International Mechanical Engineering Congress and Exposition. ASMEDC, 2002. http://dx.doi.org/10.1115/imece2002-33604.
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Mechanical stimuli are known to regulate the morphology and differentiated function of connective tissue cells. In particular, hydrostatic pressure has been reported to alter cytoskeletal organization in osteoblast-like cells (1) and chondrocytes (2), and to modulate metabolic activity in both chondrocytes (3–5) and intervertebral disc cells (6). The cellular response to continuous hydrostatic pressure is generally catabolic (3) while intermittent hydrostatic pressure at frequencies ranging from 0.25–1.0 Hz (3–5) is anabolic, giving rise to increased expression and biosynthesis of extracellular matrix (ECM) components. Previously, human dermal fibroblasts in monolayer culture were shown to respond to hydrostatic pressure by increasing heat shock protein expression levels (7). In this study, we characterize the effects of intermittent hydrostatic pressure on gene expression in human dermal fibroblasts seeded in three-dimensional polymer scaffolds.
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Marshall, Lauren, Isabel Löwstedt, Paul Gatenholm, and Joel Berry. "Prevascularized, Co-Culture Model for Breast Cancer Drug Development." In ASME 2012 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2012. http://dx.doi.org/10.1115/sbc2012-80409.
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The objective of this study was to create 3D engineered tissue models to accelerate identification of safe and efficacious breast cancer drug therapies. It is expected that this platform will dramatically reduce the time and costs associated with development and regulatory approval of anti-cancer therapies, currently a multi-billion dollar endeavor [1]. Existing two-dimensional (2D) in vitro and in vivo animal studies required for identification of effective cancer therapies account for much of the high costs of anti-cancer medications and health insurance premiums borne by patients, many of whom cannot afford it. An emerging paradigm in pharmaceutical drug development is the use of three-dimensional (3D) cell/biomaterial models that will accurately screen novel therapeutic compounds, repurpose existing compounds and terminate ineffective ones. In particular, identification of effective chemotherapies for breast cancer are anticipated to occur more quickly in 3D in vitro models than 2D in vitro environments and in vivo animal models, neither of which accurately mimic natural human tumor environments [2]. Moreover, these 3D models can be multi-cellular and designed with extracellular matrix (ECM) function and mechanical properties similar to that of natural in vivo cancer environments [3].
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Ramdhan Mhammed, Hamdan. ""Requirements for promoting a culture of peaceful coexistence and inclusion In the city of Mosul An analytical study from a social perspective "." In Peacebuilding and Genocide Prevention. University of Human Development, 2021. http://dx.doi.org/10.21928/uhdicpgp/3.
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" The current research aims to identify the nature and reality of peaceful coexistence in the city of Mosul, by determining its levels and assessing its social dimensions among its various components in the city, for the purpose of reaching the possibility of developing the feelings of its members and activating their role in achieving harmony and harmony, accepting the other, living in luxury, etc. Positive in providing stability and social and political security and identifying the resulting problems. As the importance of this research is revealed in revealing the basic dimensions of peaceful coexistence between the various social components in the city of Mosul and identifying the manifestations of these dimensions and their factors depending on measuring the extent of the cohesion of individuals and accepting or rejecting coexistence among them. This is because identifying this reality and the dimensions, manifestations and factors that support and affect it and are related to it would facilitate the consolidation of its activities and social relations between these social components in the social reality of the city. Not to mention that, the contemporary Iraqi street, specifically the city of Mosul after the American occupation of Iraq, witnessed problems and disturbances that humanity has not witnessed throughout the history of its civilized development, which affected social construction, and these problems crystallized and were born due to several reasons and accumulated reasons and silence their shape and content in the Iraqi scene, so the individuals in the city. They are more influential because they are more interacting with each other in social reality, and it is from these bases that the importance of the subject we are studying comes from. "
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Pfund, William P., Paul Neeb, and Kalan M. McPherson. "Abstract 4239: Recapitulation of human tumorsin vitro: long-term culture of heterogeneous tumor cell populations in 3-dimensions." In Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL. American Association for Cancer Research, 2012. http://dx.doi.org/10.1158/1538-7445.am2012-4239.
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Shurbaji, Samar, Ahmed Elzatahry, and Huseyin Yalcin. "The Influence of Shear Stress on Nanomaterials uptake by MDA-231 Breast Cancer Cells." In Qatar University Annual Research Forum & Exhibition. Qatar University Press, 2020. http://dx.doi.org/10.29117/quarfe.2020.0173.
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Introduction: Recently, nanotechnology products have been used for a variety of applications including the medical field. Two-dimensional (2D) nanomaterials have attracted a growing interest due to its unique properties and ultrathin structure. One common example is MXene, which can be used for cancer photothermal therapy. Methodology: In this study, two 2D nanomaterials, MXene and MXene/Au nanocomposite were fabricated as photothermal agents. To mimic physiological tumor microenvironment, nanocomposites were tested on MDA-231 breast cancer cells under fluid shear stress (~ 0.1 Dyn/cm2 ) using a perfusion setup. The uptake of these nanomaterials was tested under fluid flow compared to static culture, to assess influence of shear stress in material uptake. The uptake was assessed using confocal microscopy, scanning electron microscopy (EDS) and transmission electron microscopy. Furthermore, viability assessment was performed after exposing the treated cells to laser at different power densities and durations by live/dead assay. Results: This study revealed that there is insignificant difference in cellular uptake under fluid flow compared to static culture. Although when exposed to PTT laser irradiation, MXene alone could increase the temperature up to 100 ° C, its cellular uptake is very low (~ 3 ug/ml) which could only increase the temperature up to 44 ° C which was not sufficient to induce protein denaturation and cellular damage. Conclusion: MXene can be a good candidate for PTT for cancer treatment, but its cellular internalization should be enhanced. This can be achieved by coating the MXene surface and labeling the material with certain ligands that is cancer cell specific.
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Pfund, William P., and Paul A. Neeb. "Abstract LB-37: A patient-derivedin vitromodel of colorectal cancer: a perfusion culture system that recapitulates patient tumor composition and structure in 3-dimensions." In 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-lb-37.
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Chakraborty, Amlan, V. R. Jala, H. Bodduluri, M. Keith Sharp, and R. Eric Berson. "Effects of Directional Oscillatory Shear Index on Endothelial Cell Proliferation and Morphology." In ASME 2010 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2010. http://dx.doi.org/10.1115/sbc2010-19626.
Full textAbstract:
The effects of hemodynamic forces on cellular responses have been studied for the last three decades. Wall shear stresses (WSS) are commonly accepted as an important factor affecting anchored cells subjected to fluid flow [1, 2]. Parallel plate flow chambers and cone and plate apparatuses, which are commonly used to generate controlled shear, are limited in that only one experimental condition can be explored at a time. On the other hand, orbital shakers can be used to investigate several cases simultaneously since many culture dishes can fit on its platform. A remaining challenge, however, is that shear generated in dishes on orbital shakers is two-dimensional, nonuniform and is oscillatory in nature, and can be described analytically [3, 4] for only a few limited conditions. In this project, computational fluid dynamics (CFD) is applied to overcome those limitations by modeling the fluid flow in an orbiting petri dish for a range of conditions. In addition, cells grown under the same flow conditions were monitored for proliferation and morphology. A new directional oscillatory shear index (DOSI) is proposed to quantify the bidirectionality of oscillating shear. Cell proliferation, area, shape index and aspect ratio were investigated for different DOSI at different shear magnitudes.