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1
Ng, Colin Uber. "STEP-enabled Force Measurement Platform of Single Migratory Cells". Thesis, Virginia Tech, 2014. http://hdl.handle.net/10919/25329.
Testo completoAbstract (sommario):
Spinneret based Tunable Engineered Parameters (STEP) Platform is a recently reported pseudo-dry spinning and non-electrospinning technique that allows for the deposition of aligned polymeric nano-fibers with control on fiber diameters and orientation in single and multiple layers (diameter: sub 100nm micron, length: mm-cm), deposition (parallelism 2.5 degrees) and spacing (microns)). A wide range of polymers such as PLGA, PLA, PS, and PU have been utilized for their unique material properties in scaffold design. In this thesis two unique bioscaffolds are demonstrated for the measurement of group cell migration for wound closure and single cell contractility force for the study of force modulation.
The wound healing assay bridges the gap between confluent reservoirs of NIH3T3 fibroblasts through arrangement of a suspended array of fibers guiding group cell migration along the fiber axis. This platform demonstrates that topographical and geometrical features of suspended fibers play a very important role in wound closure. Spacing, alignment and orientation were optimized to shown an increased rate of closure. In the second complementary assay, we report a fused-fiber network of suspended fibers capable of measuring single cell forces. Results from our experiments demonstrate that force behavior is dependent on mechanical properties such as stiffness and geometry of fiber networks. We also demonstrate changes in spatial and temporal organization of focal adhesion zyxin in response to single cell migration on these networks.Master of Science
2
Tanis, Mehmet Celaleddin. "Prestack split-step fourier depth migration algorithms and parallel implementations on Cray T3E /". Digital version accessible at:, 1998. http://wwwlib.umi.com/cr/utexas/main.
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3
Jacobs, Albert. "Transport bactérien en milieu poreux : expérimentations et modélisation : migration de bactéries issues de boues de STEP". Avignon, 2007. http://www.theses.fr/2007AVIG0610.
Testo completoAbstract (sommario):
L’étude du transport bactérien en milieux poreux est un enjeu important pour la protection des nappes phréatiques contre des contaminations microbiologiques. La pratique d’épandage des effluents des stations d’épuration est une source de bactéries pathogènes dont le déplacement dans le sol constitue un risque pour la santé publique. Le transport d’une bactérie dans un milieu poreux résulte d’une compétition entre processus de déplacement, d’adhésion et de blocage. Des expériences avec une large gamme de bactéries aux propriétés de surface différentes (composantes de la tension de surface et charges) ont été réalisées pour essayer de relier ces propriétés à leur rétention en milieu poreux. Les résultats montrent que les cinétiques de rétention sont corrélées aux interactions électrostatiques mais qu’il ne semble pas y avoir de corrélation entre l’énergie libre totale d’interaction et la quantité de bactéries retenues. L’observation in situ par microscopie confocale du déplacement de cellules d’Escherichia coli a mis en évidence le coinçage des cellules bactériennes par des rugosités de surface et les zones de contact entre grains d’un milieu poreux. Ces résultats confirment l’existence de possibilités de rétention en milieux poreux même en présence de conditions défavorables (énergie libre totale d’interaction positive). Des expériences de transport avec Escherichia coli conduites dans des milieux poreux se différentiant par leur porosité et physico-chimie ont été utilisées pour évaluer le poids respectif des phénomènes de transport et d’adhésion dans la migration de cellules et pour tester un modèle de transport. La restitution des courbes d’élution observées a requis la prise en compte de deux types de détachements des cellules retenues. Les cellules retenues par les interactions de faibles intensités (Lifshitz-van der Waals) peuvent se décrocher sous l’effet des forces hydrodynamiques ou par des répulsions électrostatiques dont la portée et l’intensité augmentent lorsque la force ionique de la solution diminue. Les cellules fortement retenues peuvent aussi se détacher mais à un rythme lent et donnent lieu à de longues traînées. Les résultats ont montré que dans les milieux homogènes le transport bactérien est principalement gouverné par les interactions électrostatiques, alors que dans des milieux présentant une porosité plus compliquée, le transport est moins dépendant des interactions électrostatiques, voire très peu influencé par celles-ci. L’étude du transport, dans un sable et dans un sol, d’une communauté bactérienne issue d’une boue de station d’épuration a montré les points suivants : i/ une forte réduction de la diversité microbienne et de la concentration bactérienne ; ii/ parmi les espèces transportées se trouvaient des coliformes fécaux ; iii/ les bactéries ayant traversé les colonnes sont chargées négativement. Ces résultats confirment le rôle important des interactions électrostatiques sur la migration de bactéries en milieux poreuxThe study of bacterial transport in porous media is an important stake for the protection of ground water resources against microbial contaminations. Disposal of waste water plants effluents is an important source of pathogenic bacteria in the environment whose displacement in the ground may cause health concerns. The transport of a bacterium in a porous matrix is subjected to a competition between displacement, adhesion and blocking processes. Experiences with a broad range of bacteria with variable cellular surface properties revealed that the transport and adhesion behaviour is not identical for all the strains but depended on their respective hydrophobic and electrophoretic cell characteristics. Bacterial adhesion in porous media prevents their transport but is not an irreversible phenomenon. A model of bacterial transport in porous media able to reproduce correctly the experimental observations required to take into account two types of cell detachments: slow and fast. The cells retained by weak interactions (Lifshitz-van der Waals) can be detached by hydrodynamic forces or electrostatic repulsions whose range and intensity increase when the ionic force of a solution decreases. These results showed also that bacterial transport relied heavily on electrostatic interactions. Transport conditions are enhanced by higher electrostatic repulsions between cells and solid surface. In situ observations of Escherichia coli cells moving through pores highlighted the wedging of the bacterial cells by surface roughness and at zones of contact between porous media grains. In homogeneous mediums such as sand bacterial transport is mainly controlled by electrostatic interactions. However in heterogeneous mediums such as a soil hydrodynamics and porosity are more important. In particular for unsaturated soils where filtration of cells by small pores considerably reduces bacterial transport. The study of the fate in sand and soil media of bacterial communities from waste water plant sludge showed that faecal coliforms were among the species able to be transported. The results of this study made it possible to define safety rules related to waste water plants effluents spreading practices
4
Al-Abdullah, Yahya. "Step Migration and Urban Integration : the Transnational Trajectory of the Dom Community from the Levant to the Northern Parisian Suburbs". Electronic Thesis or Diss., Paris, EHESS, 2024. http://www.theses.fr/2024EHES0097.
Testo completoAbstract (sommario):
Mon projet de recherche traite des déplacements forcés, la migration par étape et de l’insertion urbaine des Doms Syriens. Les Doms Syriens sont une minorité ethnique présente au Levant caractérisé par une forte marginalisation et précarité, un statut d'apatride, et un mode de vie semi-nomadique. Depuis 2012, une grande partie de cette communauté à quitter la Syrie pour s'installer d'abord en Turquie et au Liban, dans des camps de réfugiés. Une partie d'entre eux a par la suite immigré en France et en Belgique à partir de 2014. Leur installation récente en région parisienne les a contraintes à s’adapter à un nouvel environnement urbain et à trouver au jour le jour les moyens de subvenir aux besoins les plus urgents : se nourrir, se loger, se repérer dans l’espace afin de pouvoir s’y déplacer. Mon analyse de leur insertion urbaine se focalise dès lors sur trois thèmes : l’économie informelle, l’habitat et les interactions avec les autorités, avec comme fil conducteur la question de l'école. En effet, l'organisation du foyer est conditionnée par la scolarisation des enfants. Ainsi, une partie centrale de mes recherches se focalise sur la scolarisation des enfants doms comme vecteur d’intégration de la communauté, et ce pour plusieurs raisons. La première est que la quasi-totalité des enfants de la communauté ne bénéficient d’aucune expérience de scolarisation antérieure à leur déplacement, en raison de la stigmatisation de leur statut social en Syrie et du long voyage qu’ils ont dû accomplir pour parvenir en France. Certaines familles ont passé plus d’un an dans cinq pays différents dont le Liban, la Mauritanie, l’Algérie, le Maroc, l’enclave espagnole au Maroc et enfin la France. La seconde raison pour laquelle mes recherches se concentrent sur la scolarisation est l’impact décisif de l’éducation à la fois sur les enfants et sur leur famille. Elle met en jeu la relation des familles avec leur voisinage et les tactiques déployées au jour le jour à travers l’économie informelle, dans laquelle la communauté dom est impliquéeMy research project deals with the forced displacement, step migration and urban integration of the Syrian Dom. The Syrian Dom are an ethnic minority present in the Levant, characterised by their strong marginalisation and precariousness, a stateless status, and a semi-nomadic lifestyle.Since 2012, a large part of this community has left Syria to settle in refugee camps in Turkey and Lebanon. Some of them subsequently immigrated to France and Belgium from 2014. Their recent settlement in the Paris region has forced them to adapt to a new urban environment, and to find the means to meet their most pressing needs on a day-to-day basis: food, housing and finding their way around the city. My analysis of their urban integration therefore focuses on three themes: the informal economy, housing and interactions with the authorities, with the question of school as a common thread. Indeed, the organization of the household is conditioned by the children's schooling.Thus, a central part of my research focuses on the schooling of Dom children as a vector of community integration, for several reasons. The first is that almost all the children in the community have no experience of schooling prior to their displacement, due to the stigmatization of their social status in Syria and the long journey they had to make to reach France. Some families have spent more than a year in five different countries, including Lebanon, Mauritania, Algeria, Morocco, the Spanish enclave in Morocco and finally France. The second reason is the decisive impact of education on both children and their families. It involves the relationship of families with their neighbourhoods and the tactics deployed on a day-to-day basis through the informal economy, in which the Dom community is involved
5
Swartling, Malin. "Brexit: A step back in Britain’s fight against human trafficking? : A comparative content analysis of the Modern Slavery Act 2015 and the EU Directive 2011/36". Thesis, Uppsala universitet, Teologiska institutionen, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-444132.
Testo completoAbstract (sommario):
Human trafficking has become an international issue of significant importance; it is the largest and most profitable organised crime after drugs and arms trafficking. Particular concern has recently been raised due to the Brexit potential ramifications on Human trafficking. There is a risk that the EU directive 2011/36 will be repealed as a result of Brexit. Accordingly, it has been questioned whether the UK national efforts and legislation concerning human trafficking are comprehensive and sufficient enough without the strengthening support of the EU and especially the EU directive 2011/36. Thus, this thesis aimed to determine the impact Brexit will have on human trafficking in the UK by investigating if there will be "gaps" in the UK national legislation on human trafficking. A comparative content analysis was conducted to analyse the UK national legislation on human trafficking, The Modern Slavery Act 2015 (MSA 2015). The Modern Slavery Act was compared with the EU directive 2011/36 to determine how the legislation differed. The method and analysis were conducted on both a latent and manifest level which means it both described the definitions and analysed how the definitions could be interpreted, hence how it affects reality. Based on what has commonly been argued the main reasons behind human trafficking in Europe, the content analysis focused on the definitions of human trafficking, prostitution and protection of migrant victims. Prostitution and migrations are frequently claimed to be the main reasons behind human trafficking in Europe. Due to the risk of the EU directive 2011/36 being repealed, the result of the thesis exhibits the need for the UK to update their national legislation. The MSA 2015 needs to become coherent with international agreements and strengthen the protection of victims of human trafficking. Due to the gendered nature of human trafficking, this research addressed human trafficking from a feminist perspective by applying the "dominance theory" and the "sameness theory". The feminist theories helped analyse and investigate the issue of human trafficking and the potential ramifications of Brexit. Applying the ideas illustrated the patriarchal structures surrounding human trafficking and within the MSA 2015.
6
Falk, Anna. "Stem cells : proliferation, differentiation, migration /". Stockholm, 2005. http://diss.kib.ki.se/2006/91-7140-497-X/.
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Erlandsson, Anna. "Neural Stem Cell Differentiation and Migration". Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl.[distributör], 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3546.
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8
Zhao, Zhiqiang. "Electric field-directed cell migration and endothelialization". Thesis, Available from the University of Aberdeen Library and Historic Collections Digital Resources. Restricted: no access until June 30, 2014, 2009. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?application=DIGITOOL-3&owner=resourcediscovery&custom_att_2=simple_viewer&pid=26544.
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9
Durand, Ellen Marie. "Regulation of hematopoietic stem cell migration and function". Thesis, Harvard University, 2014. http://dissertations.umi.com/gsas.harvard:11550.
Testo completoAbstract (sommario):
Hematopoietic stem cell transplantation (HSCT) is an effective treatment for blood disorders and autoimmune diseases. Following HSCT, these cells must successfully migrate to the marrow niche and replenish the blood system of the recipient. This process requires both non-cell and cell-autonomous regulation of hematopoietic stem and progenitor cells (HSPCs). A transgenic reporter line in zebrafish allowed the investigation of factors that regulate HSPC migration and function. To directly observe cells in their endogenous microenvironment, confocal live imaging was used to track runx1:GFP+ HSPCs as they arrive and lodge in the niche. A novel cellular interaction was observed that involves triggered remodeling of perivascular endothelial cells during niche formation. A chemical screen identified the TGF-beta pathway as a regulator of HSPC and niche interactions. Chemical manipulation of HSPCs was used to improve engraftment and repopulation capability following transplantation. Runx1:GFP fish treated with prostaglandin E2 (PGE2) during embryogenesis exhibit increased runx1+ cells in the AGM and CHT, consistent with previous in situ data. This increase in HSPCs is maintained into adulthood, even in the absence of prolonged PGE2 exposure. Kidney marrow from these treated fish can outcompete control marrow in transplantation assays. The ability of PGE2 to confer a long-term advantage on sorted mouse marrow populations in competitive transplantation assays was tested. I found that PGE2-treated short-term (ST)-HSCs, but not long-term (LT)-HSCs show enhanced transplantability in recipients compared to control animals. My studies demonstrate that the effects of PGE2 on HSC function persist over substantial time despite transient exposure. A population of short-term HSCs can engraft and give rise to long-term multilineage reconstitution following PGE2 treatment. Collectively, our studies have led to novel insights regarding the pathways involved in HSC migration, homing, and repopulation.
10
Arocena, Miguel. "Control of neural stem cell migration by electric fields". Thesis, University of Aberdeen, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.540498.
Testo completoAbstract (sommario):
Neural stem cells showed strong electrotaxis, evidenced by highly directed migration towards the cathode. Optimal electrotaxis was found to require growth factors and phosphoinositide 3-kinase (PI3-K) signalling, although reduced electrotaxis could be obtained without growth factors at the highest EFs used. After EF exposure, neural stem cell trajectories became much more linear, and a reduction in the number of cell protrusions oriented towards the anode was observed. Also, protrusions initially orienting towards the cathode retracted after the polarity of the EF was reversed, suggesting that EFs could inhibit the extension of anodal protrusions. A simple model of neural stem cell migration was built with only two key parameters, which reproduced accurately neural stem cell migration patterns, and predicted that PI3-K functions in electrotaxis mainly by controlling cell orientation. Finally, wild-type and Pax6-/- embryonic neural stem cells were exposed simultaneously to EFs and contact guidance cues in conflicting orientations. Only wild-type neural stem cells showed significant integrative migratory responses, suggesting that Pax6 is important for integration of diverse guidance cues during cell migration. The results obtained in this thesis show that neural stem cells display strong electrotaxis in vitro, which is accompanied by a qualitative change in the pattern of migration. The results also identify the control of protrusion orientation by EFs as an important element in neural stem cell electrotaxis, contributing insight into the mechanisms of electrotaxis. Finally, these results warrant further studies to assess the possibility of using EFs in brain repair therapies.
11
Tsaknakis, Grigorios. "Molecular mechanisms of stem cell migration, homing and engraftment". Thesis, University of Oxford, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.497129.
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Wedgwood, Erika Frances. "Migration of dipterous stem-borers between grasses and cereals". Thesis, University of Cambridge, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.335229.
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Alanazi, Asma. "Studies of recruitment and migration of mesenchymal stem cells". Thesis, University of Birmingham, 2016. http://etheses.bham.ac.uk//id/eprint/7112/.
Testo completoAbstract (sommario):
Mesenchymal stem cells (MSC) are used in therapy by injection into the blood. Adhesion and migration from flowing blood may be critical steps for their recruitment in the microvasculature. We aimed to understand how MSC from different sources might 'home' to injured tissue. MSC from Wharton’s jelly(WJMSC), bone marrow(BMMSC) or trabecular bone(TBMSC) were suspended in culture medium or added to whole blood, and perfused through capillaries coated with matrix proteins (collagen or fibronectin)or P- or E-selectin. Initial comparisons showed that none of the isolated MSC adhered to selectins even at low shear rate. All of the different cells were able to adhere to collagen or fibronectin at wall shear rates up to about 70s-1, with adhesion in the order WJMSC > BMMSC > TBMSC. Although BMMSC spread more efficiently than WJMSC, the WJMSC migrated faster through 8μm pore filters. In whole blood, MSC failed to bind to fibronectin, while the fibronectin itself became covered in a single layer of spread platelets. When perfused over collagen, only WJMSC were found to attach, forming aggregates with platelets on the surface. Adhesion of MSC to matrix proteins and to platelets involved both β1- and β3-integrins. Platelets used glycoproteins GpIb and GpIIbIIIa to adhere and aggregate on collagen, and GpIIbIIIa to adhere and spread on fibronectin, but these receptors did not support the interaction between MSC and platelets. These results show intrinsic differences in adhesion and migration of different MSC, including interaction with platelets that are predicted to influence their behavior in vivo and therapeutic effectiveness.
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Wimmer, Ryszard. "Migration of neural stem cells during human neocortical development". Electronic Thesis or Diss., Université Paris sciences et lettres, 2024. http://www.theses.fr/2024UPSLS016.
Testo completoAbstract (sommario):
Chez les espèces gyrencéphaliques, et en particulier chez l'homme, la forte augmentation de la taille du néocortex est largement soutenue par une niche neurogénique élargie, la zone sous-ventriculaire externe (oSVZ). Cela est dû en grande partie à l'amplification d'une population de cellules souches neurales, les cellules gliales radiales basales (bRG, également appelées oRG). Les cellules bRG colonisent la zone sous-ventriculaire externe grâce à un mouvement dépendant de l'acto-myosine appelé translocation somale mitotique (MST). Le mécanisme moléculaire exact de la MST, la question de savoir si le cytosquelette des microtubules contrôle également d'autres étapes de la translocation des cellules bRG et la contribution de ces mouvements à la dissémination des cellules bRG dans le néocortex humain en développement sont toutefois inconnus. Ici, en utilisant l'imagerie en direct du tissu fœtal humain de la semaine 14-21 et des organoïdes cérébraux, nous identifions un mode de translocation en deux étapes pour les cellules bRG. En plus de la TMS, les cellules bRG subissent un mouvement dépendant des microtubules pendant l'interphase, que nous appelons translocation somale interphasique (TSI). L'IST est plus lente que la TMS et contrôlée par le complexe LINC qui recrute le moteur moléculaire dynéine et son activateur LIS1 vers l'enveloppe nucléaire pour le transport. Par conséquent, le TSI est affecté dans les organoïdes dérivés de patients LIS1. Nous montrons en outre que la TMS se produit pendant la prométaphase et qu'il s'agit donc d'un événement de translocation du fuseau mitotique. Le TSI et le TMS sont tous deux bidirectionnels, avec un mouvement basal net de 0,57 mm par mois de gestation du fœtus humain.Nous montrons que 85% de ce mouvement dépend de l'IST, qui est à la fois plus polarisé et plus processif que le MST.Enfin, nous démontrons que l'IST et le MST sont conservés dans les cellules de glioblastome liées à bRG et qu'ils interviennent par les mêmes voies moléculaires. Dans l'ensemble, notre travail identifie comment les cellules bRG colonisent le cortex fœtal humain et comment ces mécanismes peuvent être liés à des conditions pathologiquesIn gyrencephalic species, and in particular in humans, the strong size increase of the neocortex is largely supported by an expanded neurogenic niche, the outer subventricular zone (oSVZ). This is largely due to the amplification of a neural stem cell population, the basal radial glial cells (bRGs, also known as oRGs). bRG cells colonize the oSVZ through an acto-myosin dependent movement called mitotic somal translocation (MST). The exact molecular mechanism of MST, whether the microtubule cytoskeleton also controls other steps of bRG cell translocation, and the contribution of these movements to bRG cell dissemination into the human developing neocortex are however unknown. Here, using live imaging of gestational week 14-21 human fetal tissue and cerebral organoids, we identify a two-step mode of translocation for bRG cells. On top MST, bRG cells undergo a microtubule-dependent movement during interphase, that we call interphasic somal translocation (IST). IST is slower than MST and controlled by the LINC complex that recruits the dynein molecular motor and its activator LIS1 to the nuclear envelope for transport. Consequently, IST is affected in LIS1 patient derived organoids. We furthermore show that MST occurs during prometaphase and is therefore a mitotic spindle translocation event. MST is controlled by the mitotic cell rounding molecular pathway, that increases the cell cortex stiffness to drive translocation. Both IST and MST are bidirectional with a net basal movement of 0,57 mm per month of human fetal gestation. We show that 85% of this movement is dependent on IST, that is both more polarized and more processive than MST. Finally, we demonstrate that IST and MST are conserved in bRG-related glioblastoma cells and occur through the same molecular pathways. Overall, our work identifies how bRG cells colonize the human fetal cortex, and how these mechanisms can be linked to pathological conditions
15
Elseed, Mohammed. "Investigation of periodontal stem cell attachment to dentin and dental pulp stem cell migration". Thesis, NSUWorks, 2007. https://nsuworks.nova.edu/hpd_cdm_stuetd/12.
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Howard, Cameron. "Regulation of dental pulp stem cell migration and regenerative endodontics". Thesis, NSUWorks, 2010. https://nsuworks.nova.edu/hpd_cdm_stuetd/8.
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17
Mahdipour, Elahe. "Haematopoietic stem/progenitor cell migration and differentiation in response to injury". Thesis, University of Manchester, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.518453.
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18
Cichon, Monika Agnieszka. "Axl regulates adhesion, migration and stem-like properties of cancer cells". Thesis, Queen Mary, University of London, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.610930.
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Sotto, David C. "Directing the migration of mesenchymal stem cells with superparamagnetic iron oxide nanoparticles". Diss., Georgia Institute of Technology, 2015. http://hdl.handle.net/1853/54897.
Testo completoAbstract (sommario):
Cell migration plays an important role in numerous normal and pathological processes. The physical mechanisms of adhesion, protrusion/extension, contractions, and polarization can regulate cell migration speed, persistence time, and downstream effects in paracrine and endocrine signaling. Methods for understanding these biophysical and biochemical responses to date have been limited to the use of external forces acting on mechanotransductive receptors. Additionally, as the use of magnetic nanoparticles for cell tracking and cell manipulation studies continues to gain popularity, so does the importance of understanding the cellular response to mechanical forces caused by these magnetic systems. This thesis work utilizes superparamagnetic iron oxide nanoparticles and static magnets to induce an endogenous magnetic force on the cell membrane. This cell manipulation model is used to better understand the mechanobiological responses of mesenchymal stem cell to SPIO labeling and endogenous force generation. Directionally persistent motility, cytoskeletal reorganization, and altered pro-migratory cytokine secretion is reported in this thesis as a response to SPIO based cell manipulation.
20
Sundström, Magnus. "Signal transduction in mast cell migration /". Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2001. http://publications.uu.se/theses/91-554-5130-6/.
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21
Yu, Jiaole, e 于皎乐. "Intrinsic and extrinsic factors affecting the migratory mechanisms of human mesenchymal stem cells". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hdl.handle.net/10722/197130.
Testo completoAbstract (sommario):
The potential applications of mesenchymal stem cells (MSCs) have been widely advocated, however, many barriers hinder their clinical utilization. Enhancement of the homing of human MSCs (hMSCs) to the target tissues remains a clinical challenge. To overcome this hurdle, the mechanisms responsible for migration and engraftment of hMSCs have to be defined. My study aimed to explore both the underlying mechanisms and means of enhancing the migration of hMSCs.
A graft versus host disease (GvHD) injury model and a novel orthotopic neuroblastoma model were established to delineate the distinct property of hMSCs homing towards either injured or cancerous tissues. This highly specific homing process was further revealed to be in a CXCR4-dependent manner.
Notably, a novel gene, exchange protein directly activated by cAMP (Epac), was demonstrated to be actively involved in the hMSCs homing process. hMSCs expressed functional Epac and its activation significantly enhanced the migration and adhesion of hMSCs. Furthermore, Epac activation directly contributed to the chemotactic response of hMSCs to SDF-1, suggesting that Epac is linked to the stromal cell derived factor-1 (SDF-1) signaling cascades. Importantly, the homing of hMSCs towards injured tissues in vivo could be dramatically increased by Epac activation.
hMSCs are adherent cells and their migration to distant tissues thus requires detachment into a suspension state. This disruption of cell-extracellular matrix interaction, known as anoikis stress, triggers programmed cell death, leading to a marked decrease in the efficiency of cell trafficking and engraftment. Anoikis stress induced massive cell death has emerged as the major challenge in the application of hMSCs. How some of the hMSCs can overcome this adversity and migrate towards distant destinations remains largely unexplored. It was observed that the surviving hMSCs circumvented anoikis stress by forming self-supporting cellular aggregates. Compared to adherent hMSCs, aggregated-hMSCs had better migratory response to both SDF-1α and SDF-1α analogue (CTCE-0214). Such enhanced migratory effect was proven to be CXCR4-dependent both in vitro and in vivo by using a CXCR4 specific antagonist (AMD3100). Although the viability of hMSCs under anoikis stress dramatically decreased, CTCE-0214 could promote cell survival and facilitate the migration of hMSCs towards injured targets. This phenomenon could be partially explained by the increase in anti-apoptosis effect via up-regulated Bcl-2 expression and autophagy activation under CTCE-0214 treatment.
The exact effects of hMSCs on tumor growth and progression have long been controversial. Significant fasten growth and promoted metastasis of neuroblastoma in vivo was observed in hMSCs co-transplanted mice in this study. Reciprocally, hMSCs could not only be recruited by primary tumor, but also be selectively attracted by metastatic loci. This recruitment was significantly reduced when hMSCs were pre-treated with AMD3100, suggesting that the SDF-1/CXCR4 axis was a prime mover in this process.
In summary, my study demonstrated that the migratory property of hMSCs could be enhanced by novel intrinsic and extrinsic factors using both in vitro and in vivo models. This study provides a new prospective on MSCs biology during the ex vivo manipulation process and I proposed means to overcome some of these hindrance so we can maximize the efficacy of clinical MSCs application in the future.published_or_final_version
Paediatrics and Adolescent Medicine
Doctoral
Doctor of Philosophy
22
Mihic, Bojana [Verfasser], Irmgard [Akademischer Betreuer] Merfort e Jochen [Akademischer Betreuer] Seufert. "Macrophage migration inhibitory factor (MIF)/CXCR4 axis in migration of mesenchymal stem cells (MSC) towards pancreatic [beta]-cells under lipotoxic conditions". Freiburg : Universität, 2017. http://d-nb.info/1179694651/34.
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Kašėta, Vytautas. "Investigation of Bone Marrow Hematopoietic Stem Cell Migration during Inflammation in BALB/c Mice". Doctoral thesis, Lithuanian Academic Libraries Network (LABT), 2011. http://vddb.laba.lt/obj/LT-eLABa-0001:E.02~2011~D_20111102_110918-10945.
Testo completoAbstract (sommario):
The aim of dissertation work to investigate the anti-inflammatory effect of murine bone marrow hematopoietic stem cells and their migration in the BALB/c mouse contact hypersensitivity model in vivo. It was found that isolated hematopoietic cell populations had a significant anti-inflammatory effect and inhibited the edema. The studies showed that the most efficient (up to 66%) inhibition of foot edema was obtained when using the HSC population. For the first time the HSC population migration kinetics in the BALB/c mouse contact hypersensitivity model in vivo was investigated. We determined that cells of this population can be found in mice paw edema and liver after just one hour. A little bit later they are detected in the spleen. We did the HSC population quantitative migration kinetic studies and found that in case of foot inflammation there is a secondary migration of the transplanted HSC migrating from the bone marrow to the spleen hematopoietic niche. We have shown that these cells selectively migrate into the inflammation areas of the foot edema. Transplanted cells quantity in the samples of foot edema, as compared with the untreated foot, was more than 1000 times higher. A transplanted hematopoietic stem cell migration research during inflammation, carried out in this work, contributes to clarification of stem cell migration patterns in case of pathological processes. This is particularly important in ensuring a safe and effective stem cell application in practice.Šio darbo tikslas ištirti pelių kaulų čiulpų hemopoetinių kamieninių ląstelių priešuždegiminį poveikį bei migraciją BALB/c pelių kontaktinio hiperjautrumo modelyje in vivo. Nustatyta, kad išskirtos hemopoetinės ląstelių populiacijos pasižymėjo efektyviu priešuždegiminiu poveikiu ir slopino edemą. Efektyviausiai (iki 66%) pėdos edemą slopino HKL populiacija. Pirmą kartą buvo ištirta HKL populiacijos migracijos kinetika BALB/c pelių kontaktinio hiperjautrumo modelyje in vivo. Nustatyta, kad šios populiacijos ląstelės jau po 1 val. aptinkamos tiriamų pelių pažeistoje pėdoje ir kepenų histologiniuose preparatuose, kiek vėliau jos aptinkamos blužnyje. Atlikti HKL populiacijos kiekybiniai migracijos kinetikos tyrimai. Nustatyta, kad esant uždegimui pėdoje vyksta transplantuotų HKL antrinė migracija iš kaulų čiulpų į blužnies hemopoetines nišas. Parodyta, kad šios populiacijos ląstelės selektyviai migruoja į uždegimo vietą pažeistoje pėdoje. Transplantuotų ląstelių kiekis pėdos edemos mėginiuose buvo daugiau nei 1000 kartų didesnis lyginant su nepaveikta pėda. Šiame darbe atlikti transplantuotų hemopoetinių kamieninių ląstelių migracijos tyrimai uždegimo metu prisideda prie kamieninių ląstelių migracijos dėsningumų išaiškinimo patologinių procesų metu, kas yra ypač svarbu užtikrinant saugų ir efektyvų kamieninių ląstelių taikymą klinikinėje praktikoje.
24
Carney, Brooke J. "Building Velocity Models for Steep-Dip Prestack Depth Migration through First Arrival Traveltime Tomography". Thesis, Virginia Tech, 2000. http://hdl.handle.net/10919/35941.
Testo completoAbstract (sommario):
Although the petroleum industry has imaged reflections from the sides of salt domes,
steeply dipping structures have not been imaged as reflectors outside of sedimentary
basins; to do so requires appropriate data acquisition, prestack depth migration, and an
excellent seismic velocity model. Poststack time migrated seismic images, normal
moveout velocity analysis, well logs, and other geologic information are used to build the
velocity model. In regions of interest outside of sedimentary basins, such as major strike-slip
faults, seismic reflectivity is often sparse and little is known of detailed subsurface
geology. Alternate methods of velocity model construction must be used. First arrival
(refraction and turning ray) traveltime tomography is proposed to construct the
preliminary velocity model for steep-dip prestack depth migration in settings with little a
priori subsurface information. A densely spaced synthetic seismic data set with long-offset
recording, modeled after a real survey across the San Andreas Fault, was
constructed using a finite-difference algorithm. First arrival traveltimes were picked
from the data and a velocity model was constructed using tomography. The velocity
model was used to perform a Kirchhoff prestack depth migration of the synthetic shot
gathers. The subsurface structure was sufficiently reconstructed that the velocity model
could be refined through migration velocity analysis. A series of tomography tests was
used to determine the spatial resolution limits of the velocity model. Isolated erroneous
anomalies with sizes near the resolution limits were added to the velocity model derived
from tomography and used as input for migration. This pessimistic test provided an
adequate image and identifiable arrivals in migrated common image gathers, allowing the
velocity model to be improved through migration moveout analysis. Data acquisition requirements for tomography include long recording offsets and times, larger sources, and dense spacings, very similar to the requirements for steep-dip reflection imaging.Master of Science
25
Kawauchi, Takeshi. "The in vivo roles of STEF/Tiam1, Rac1 and JNK in cortical neuronal migration". Kyoto University, 2004. http://hdl.handle.net/2433/147523.
Testo completo
26
Kollar, Katarina. "The molecular mechanisms utilised by mesenchymal stem cells in migration to acute myocardial infarction". Thesis, Queensland University of Technology, 2010. https://eprints.qut.edu.au/41698/1/Katarina_Kollar_Thesis.pdf.
Testo completoAbstract (sommario):
Heart damage caused by acute myocardial infarction (AMI) is a leading cause of death and disability in Australia. Novel therapies are still required for the treatment of this condition due to the poor reparative ability of the heart. As such, cellular therapies that assist in the recovery of heart muscle are of great current interest. Culture expanded mesenchymal stem cells (MSC) represent a stem and progenitor cell population that has been shown to promote tissue recovery in pre-clinical studies of AMI. For MSC-based therapies in the clinic, an intravenous route of administration would ideally be used due to the low cost, ease of delivery and relative safety. The study of MSC migration is therefore clinically relevant for a minimally invasive cell therapy to promote regeneration of damaged tissue. C57BL/6, UBI-GFP-BL/6 and CD44-/-/GFP+/+ mice were utilised to investigate mMSC migration. To assist in murine models of MSC migration, a novel method was used for the isolation of murine MSC (mMSC). These mMSC were then expanded in culture and putative mMSC were positive for Sca-1, CD90.2, and CD44 and were negative for CD45 and CD11b. Furthermore, mMSC from C57BL/6 and UBI-GFP-BL/6 mice were shown to differentiate into cells of the mesodermal lineage. Cells from CD44-/-/GFP+/+ mice were positive for Sca-1 and CD90.2, and negative for CD44, CD45 and CD11b however, these cells were unable to differentiate into adipocytes and chondrocytes and express lineage specific genes, PLIN and ACAN. Analysis of mMSC chemokine receptor (CR) expression showed that although mMSC do express chemokine receptors, (including those specific for chemokines released after AMI), these were low or undetectable by mRNA. However, protein expression could be detected, which was predominantly cytoplasmic. It was further shown that in both healthy (unperturbed) and inflamed tissues, mMSC had very little specific migration and engraftment after intravenous injection. To determine if poor mMSC migration was due to the inability of mMSC to respond to chemotactic stimuli, chemokine expression in bone marrow, skin injury and hearts (healthy and after AMI) was analysed at various time points by quantitative real-time PCR (qRT PCR). Many chemokines were up-regulated after skin biopsy and AMI, but the highest acute levels were found for CXCL12 and CCL7. Due to their high expression in infarcted hearts, the chemokines CXCL12 and CCL7 were tested for their effect on mMSC migration. Despite CR expression at both protein and mRNA levels, migration in response to CXCL12 and CCL7 was low in mMSC cultured on Nunclon plastic. A novel tissue culture plastic technology (UpCellTM) was then used that allowed gentle non-enzymatic dissociation of mMSC, thus preserving surface expression of the CRs. Despite this the in vitro data indicated that CXCL12 fails to induce significant migration ability of mMSC, while CCL7 induces significant, but low-level migration. We speculated this may be because of low levels of surface expression of chemokine receptors. In a strategy to increase cell surface expression of mMSC chemokine receptors and enhance their in vitro and in vivo migration capacity, mMSC were pre-treated with pro-inflammatory cytokines. Increased levels of both mRNA and surface protein expression were found for CRs by pre-treating mMSC with pro-inflammatory cytokines including TNF-á, IFN-ã, IL-1á and IL-6. Furthermore, the chemotactic response of mMSC to CXCL12 and CCL7 was significantly higher with these pretreated cells. Finally, the effectiveness of this type of cell manipulation was demonstrated in vivo, where mMSC pre-treated with TNF-á and IFN-ã showed significantly increased migration in skin injury and AMI models. Therefore this thesis has demonstrated, using in vitro and in vivo models, the potential for prior manipulation of MSC as a possible means for increasing the utility of intravenously delivery for MSC-based cellular therapies.
27
李晓 e Xiao Li. "Macrophage migration inhibitory factor and circulating progenitor cells: relevance and implications inperiodontal medicine". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B45894267.
Testo completo
28
Tan, Yew Liang Terence Clinical School St George Hospital Faculty of Medicine UNSW. "Differentiation and migration of Sca-1+/CD 31-cardiac side population cells in a mouse infarction model". Publisher:University of New South Wales. Clinical School - St George Hospital, 2009. http://handle.unsw.edu.au/1959.4/43387.
Testo completoAbstract (sommario):
Myocardial infarction is the most common cause of heart failure and remains one of the leading causes of morbidity and mortality in humans. Stem cells are important in the maintenance and repair of adult tissues. Hoechst effluxing cells, termed side population cells are a rare subset of cells found in adult tissues that are highly enriched for stem and progenitor cell activity. Recent studies have suggested that Sca-1+/CD31- cardiac side population cells are capable of differentiation into cardiomyocytes in vitro. However, the response of cardiac side population cells to myocardial injury remains unknown in vivo. In this study, we directly transplanted Sca-1+/CD31- cardiac side population cells into an acutely infarcted mouse heart. After two weeks, the transplanted cells were found to express cardiomyocyte or endothelial cell markers. Importantly, when these cells were transplanted into a remote nonischemic part of the heart after MI, they were able to migrate to the damaged myocardium. Consistent with these cells homing property, we found that SDF-1α, a chemotactic chemokine and its receptor, CXCR4 were up-regulated in the damaged myocardium and on Sca-1+/CD31- cardiac SP cells respectively following an acute myocardial infarction. We further showed that SDF-1α was able to induce migration of Sca-1+/CD31- cardiac side population cells in vitro. Our results have therefore suggested that Sca-1+/CD31- cardiac side population cells are able to migrate to damaged myocardium from non-ischemic myocardium and differentiate into cardiomyocytes as well as endothelial cells in the acutely infarcted mouse heart. We postulate that the SDF-1α/CXCR4 interaction may play an important role in the migration of these cells. Understanding and enhancing these processes may hold enormous potential possibilities for therapeutic myocardial regeneration for the treatment of cardiovascular disease.
29
Rooney, Claire. "A role for the Rac GEF, STEF, in cell migration, polarization and Ras-induced transformation". Thesis, University of Manchester, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.492898.
Testo completoAbstract (sommario):
Tiam1 (for T-lymphoma invasion and metastasis-inducing protein) belongs to the Rho GEF family of proteins. In response to growth factors and cell-substrate interactions, Tiam1 selectively activates Rac. Using a two stage chemical carcinogenesis protocol (DMBA/TPA) it was previously shown that mice lacking Tiam1 are resistant to the development of Ras-induced skin tumours, suggestmg an important role for Tiam1/Rac signalling in tumourigenesis in vivo.
30
Pesaresi, Martina 1991. "Exogenous expression of chemokine receptors improves mouse mesenchymal stem cell migration towards the degenerating retina". Doctoral thesis, TDX (Tesis Doctorals en Xarxa), 2019. http://hdl.handle.net/10803/672991.
Testo completoAbstract (sommario):
Retinopathies are a heterogeneous group of conditions that inevitably lead to vision incapacitation and blindness. Currently, they are incurable. Cell therapy has been proposed as a potential solution, but further development and optimization are required. In particular, this study addresses the problem of inadequate migration and integration of transplanted cells into the host tissue. In fact, the majority of the cells transplanted in the eye are unable to reach the injury site, where they are most needed. Hence, we hypothesize that improving cells’ migratory ability could appreciably enhance the therapeutic outcome of transplantation-based strategies.
After identifying the chemokines that are most upregulated during retinal degeneration, we have over-expressed the corresponding receptors on mouse mesenchymal stem cells. Overall, we found that combined exogenous expression of two specific chemokine receptors significantly improves both ex vivo and in vivo migration of mouse mesenchymal stem cells.
The strategy explored in this study provides a way to generate ad hoc engineered stem cells with an increased responsiveness to retina-specific signals. Ultimately, our findings could be integrated with alternative optimization strategies to make stem cell therapy in the eye a feasible and realistic option for the treatment of retinopathies, and for the achievement of visual restoration.Las retinopatías representan un grupo heterogéneo de enfermedades que causan, de forma inevitable, discapacidad visual y ceguera. En la actualidad no se dispone de una cura para estas enfermedades para las que la terapia celular podría ser una solución válida, en el caso de que ésta pudiera ser mejorada y optimizada. El presente estudio enfrenta el problema de la escasa e inadecuada migración de las células trasplantadas en el tejido diana. De hecho, la mayoría de las células trasplantadas en el globo ocular no consiguen llegar allí donde se las requiere; donde se encuentra la lesión. Por este motivo, se plantea la hipótesis de que mejorar la capacidad migratoria de las células podría resultar en una mejora substancial del resultado terapéutico de los trasplantes celulares. Después de identificar las quimiocinas más expresadas durante la degeneración de la retina, se ha procedido a sobre-expresar los receptores correspondientes en células madre mesenquimales de ratón. En general, los resultados obtenidos indican que la expresión exógena combinada de dos receptores específicos de quimiocinas mejoran significativamente la migración de células madre mesenquimales, tanto ex vivo como in vivo. La estrategia desarrollada en este estudio proporciona una forma de generar células madre con una mayor capacidad de respuesta a señales específicas de la retina. Tanto es así, que los hallazgos que en él se detallan podrían integrarse con otras estrategias de optimización, de forma que la terapia con células madre sea una opción factible y realista para el tratamiento de retinopatías.
31
Draheim, Kyle M. "An Integral Role of ARRDC3 in Stem Cell Migration and Breast Cancer Progression: A Dissertation". eScholarship@UMMS, 2010. https://escholarship.umassmed.edu/gsbs_diss/468.
Testo completoAbstract (sommario):
Despite the importance of integrins in epithelial cell biology surprisingly little is known about their regulation. It is known that they form hemidesmosomes (HDs), are actively involved in cell contacts during cell migration/invasion, and are key signaling molecules for survival and growth. However, there has been a distinct lack of understanding about what controls the dynamic integrin localization during cell activation and movement. Growth factors, such as EGF, are elevated during wound healing and carcinoma invasion leading to phosphorylation of ITGβ4 and the disassembly of the HD and mobilization of ITGβ4 to actin-rich protrusions. More recently the phosphorylation of a novel site on ITGβ4 (S1424) was found to be distinctly enriched on the trailing edge of migrating cells, suggesting a possible mechanism for the dissociation of ITGβ4 from HDs.
Arrestin family member proteins are involved in the regulation of cell surface proteins and vesicular trafficking. In this study, we find that over-expression of arrestin family member ARRDC3 causes internalization and proteosome-dependent degradation of ITGβ4, while decreased levels of ARRDC3 stabilizes ITGβ4 levels. These results lead us to a new mechanism of ITGβ4 internalization, trafficking and degradation. During migration, ARRDC3 co-localizes with ITGβ4 on the lagging edge of cells but has a distinct distribution on the leading edge of cells. Additional immuno co-precipitation experiments demonstrate that ARRDC3 preferentially binds to ITGβ4 when phosphorylated on S1424. Using confocal microscopy, we show that the expression pattern of ARRDC3 on the lagging edge of a migrating cell is identical to the expression pattern of ITGβ4-pS1424. We demonstrate that ARRDC3 expression represses cell proliferation, migration, invasion, growth in soft agar and tumorigenicity.
Collectively, our data reveals that ARRDC3 is a negative regulator of β4 integrin and demonstrates how this new pathway impacts biologic processes in stem cell and cancer biology. Additionally, as ARRDC3 is highly expressed in several tissues and conserved across species, our results are likely to be translated to other models.
32
Badr, Gelan. "Modeling First -Year Engineering Retention Rate and Success in STEM at Youngstown State University". Youngstown State University / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=ysu1402375615.
Testo completo
33
Wong, Hoi-ling, e 王凱玲. "Migration and other characteristics of collagen microencapsulated hMSCs: a comparison with hMSCs intraditional 2D culture". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B4150902X.
Testo completo
34
Ford, Catriona Barbara. "CX3CR1/CX3CL1 axis drives the migration and maturation of oligodendroglia in the central nervous system". Thesis, University of Edinburgh, 2017. http://hdl.handle.net/1842/29533.
Testo completoAbstract (sommario):
In the central nervous system, the axons of neurons are protected from damage and aided in electrical conductivity by the myelin sheath, a complex of proteins and lipids formed by oligodendrocytes. Loss or damage to the myelin sheath may result in impairment of electrical axonal conduction and eventually to neuronal death. Such demyelination is responsible, at least in part, for the disabling neurodegeneration observed in pathologies such as Multiple Sclerosis (MS) and Spinal Cord Injury. In the regenerative process of remyelination, oligodendrocyte precursor cells (OPCs), the resident glial stem cell population of the adult CNS, migrate toward the injury site, proliferate and differentiate into adult oligodendrocytes which subsequently reform the myelin sheath. Existing research indicates that OPC migration is directed by chemomigratory signals released from the site of injury and that the absence of OPCs is a feature of some MS lesions, suggesting that increased recruitment of OPCs to injury sites might improve remyelination, eventually leading to treatments of patient pathologies. I hypothesized that as yet undiscovered migration cues for OPCs might be released at sites of demyelination, diffuse through the CNS tissue, activate distal OPCs and guide them back to sites of demyelination. In this thesis, I performed bioinformatics analysis of gene expression arrays and identified upregulated cell surface receptors on OPCs activated in a cuprizone model, and upregulated secreted factors in whole lesion sites from an LPC induced MS type injury model and a Spinal Cord Injury model. I then optimised the X-celligence system for the quantification of OPC migration in response to secreted factors identified in my bioinformatics screen. By combination of these techniques with immunofluorescent staining I discovered novel expression of the cell surface receptor CX3CR1 on OPCs, increased expression of the corresponding ligand CX3CL1 in both MS type injury and Spinal Cord Injury, increased directional migration of OPCs in response to low concentrations of CX3CL1, and increased maturation of OPCs into adult oligodendrocytes at high concentrations of CX3CL1. Taken together these results propose a system in which an increasing gradient of CX3CL1 released from the site of injury directs the recruitment, then maturation of OPCs, making CX3CL1 a master regulator of OPC led CNS regeneration.
35
Wong, Hoi-ling. "Migration and other characteristics of collagen microencapsulated hMSCs a comparison with hMSCs in traditional 2D culture /". Click to view the E-thesis via HKUTO, 2008. http://sunzi.lib.hku.hk/hkuto/record/B4150902X.
Testo completo
36
Koch, Britta. "Scaffold dimensionality and confinement determine single cell morphology and migration". Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2016. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-194717.
Testo completoAbstract (sommario):
This thesis describes a highly interdisciplinary approach to discern the differing impact of scaffold dimensionality and physical space restrictions on the behavior of single cells. Rolled-up nanotechnology is employed to fabricate three-dimensional (3D) SiO/SiO2 microtube geometries of varied diameter, that after a biofunctionalization step are shown to support the growth of U2OS and six different types of stem cells. Cell confinement quantifiable through the given microtube diameter is tolerated by U2OS cells through a remarkable elongation of the cell body and nucleus down to a certain threshold, while the integrity of the DNA is maintained.
This confinement for NSPCs also leads to the approaching of the in vivo morphology, underlining the space-restrictive property of live tissue. The dimensionality of the cell culture scaffold however is identified as the major determiner of NSPC migration characteristics and leads to a morphologically distinct mesenchymal to amoeboid migration mode transition. The 3D microtube migration is characterized by exclusively filopodia protrusion formation, a higher dependence on actin polymerization and adopts aspects of in vivo-reported saltatory movement. The reported findings contribute to the determination of biomaterial scaffold design principles and advance our current understanding of how physical properties of the extracellular environment affect cell migration characteristics.
37
Pappou, Emmanouil. "The role of IKK2 in TNF-alpha-induced migration and proliferation of human mesenchymal stem cells". Diss., lmu, 2012. http://nbn-resolving.de/urn:nbn:de:bvb:19-143859.
Testo completo
38
Evans, Corey. "THE EFFECTS OF SDF-1α TREATMENT ON THE MIGRATION OF NEURAL STEM/PROGENITOR CELLS AFTER TRAUMATIC BRAIN INJURY". VCU Scholars Compass, 2011. http://scholarscompass.vcu.edu/etd/2486.
Testo completoAbstract (sommario):
Traumatic Brain Injury (TBI) is one of the leading causes of death and disability among young adults and has been a significant field in medical research over the past decades. Intensive studies focusing on how to repair tissue damage resulting from head injuries have discovered that the central nervous system (CNS) retains a regenerative capacity throughout life due to the persistent presence of neural stem/progenitor cells (NS/NPCs) in the neurogenic regions. In the normal brain, cells generated in the subventricular zone (SVZ) migrate along the rostral migratory stream (RMS) to the olfactory bulb and cells in the subgranular zone (SGZ) migrate laterally into the granule cell layer of the dentate gyrus. Directed movement of these NS/NPCs is controlled by a variety of factors, and among them the chemoattractant SDF-1 is of particular importance. Studies have identified that the chemokine SDF-1α and its receptor CXCR4 play an important role in guiding cell migration in many types of cells including NS/NPCs. The current study tested if SDF-1 could be delivered through alginate to attract and guide migration of NS/NPCs and its progeny both in vitro and in vivo. Using a Boyden chamber migration assay, we found SDF-1α either added directly in the medium or incorporated into alginate threads was capable of influencing migration of cultured NS/NPCs in a dose-dependent manner. In the in vivo study, when injected directly into the cerebral cortex, SDF-1 showed limited capability in inducing neuroblasts migration off the normal tract to the site of SDF-1 injection. When SDF-1 was delivered via alginate thread to the focal injury site at 2 days post TBI, significantly increased number of migrating neuroblasts derived from the SVZ was observed around the injury site. Increased expression of SDF-1 receptor CXCR4 was observed in the NS/NPCs in the SVZ and around the injury site following TBI. These data suggest that bioactive SDF-1α can be delivered via alginate thread and exogenous delivery of SDF-1α and its interaction with receptor CXCR4 mediates migration of newly generated neurons from the SVZ to the site of injury following TBI. Collectively, our study indicates that SDF-1α could be utilized as a guidance cue for tissue repair following brain injury.
39
Eiriz, Maria Francisca Santos. "Migration and differentiation of neuronal precursors in the postnatal brain: insights from the subventricular zone and cerebellum". Doctoral thesis, Faculdade de Ciências e Tecnologia, 2013. http://hdl.handle.net/10362/11447.
Testo completoAbstract (sommario):
Fundação para a Ciência e a Tecnologia - SFRH/BD/42848/2008, através do Programa MIT_Portugal em Sistemas de Bioengenharia; projectos PTDC/SAUNEU/104415/2008 e Projecto ref. 96542 da Fundação Caloust Gulbenkian
40
Vrotsos, Emmanuel George. "MCP-1 and APP involvement in glial differentiation and migration of neuroprogenitor cells". Orlando, Fla. : University of Central Florida, 2009. http://purl.fcla.edu/fcla/etd/CFE0002517.
Testo completo
41
Falzon, Kevin [Verfasser], Eric [Akademischer Betreuer] Bodden, Bernd [Akademischer Betreuer] Freisleben e Patrick [Akademischer Betreuer] Eugster. "On the Use of Migration to Stop Illicit Channels / Kevin Falzon ; Eric Bodden, Bernd Freisleben, Patrick Eugster". Darmstadt : Universitäts- und Landesbibliothek Darmstadt, 2017. http://d-nb.info/112415518X/34.
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42
Pepperell, Emma E. "The regulation of stem cell engraftment". Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:873a14b9-6c7b-4643-bb34-4e1679d4f734.
Testo completoAbstract (sommario):
The engraftment of haemopoietic stem/progenitor cells (HSPCs) from umbilical cord blood (UCB) into adult recipients, although advantageous in terms of sourcing units, the decreased need to match donor and recipient and reduced risk of graft versus host disease (GvHD), is delayed compared to grafts using HSPCs from mobilised peripheral blood (MPB) or bone marrow (BM). One reason for this is the limited number of HSPCs (CD34+/CD133+ cells) in a unit of UCB compared to MPB or BM. The CXCR4-CXCL12 axis is widely recognised as a key player in the bone marrow homing, retention, and engraftment of HSPCs. The aim of this thesis was to investigate whether the engraftment of HSPCs from UCB into the bone marrow could be improved. Firstly, a novel in vitro 3D time-lapse chemotaxis assay to assess the homing capacity of human UCB CD133+ HSPCs, towards the chemokine CXCL12 was developed. One advantage of this assay was that it distinguished cell chemotaxis from chemokinesis and allowed these parameters to be quantified. Human UCB CD133+ HSPC chemotaxis towards CXCL12 was inhibited by the CXCR4 antagonist, AMD3100. Importantly, the presence of CXCL12 or AMD3100 had no affect on cell chemokinesis. To complement the in vitro chemotaxis assay, a short term in vivo homing assay in NSG mice was successfully established. The effect of siRNA silencing of the CXCR4 co-receptor, CD164, which is also expressed on CD133+ HSPCs, on cell migratory and homing ability was investigated. CD164 knock-down using siRNA in human UCB CD133+ HSPCs did not demonstrate an effect on homing to NSG bone marrow in vivo or chemotaxis to CXCL12 in vitro. However, homing to NSG mouse spleen was significantly reduced in cells silenced for CD164. Following this, an 8 day HSPC expansion system using nanofibre scaffolds (Nanex) and differing cytokines was investigated. These serum and feeder free conditions yielded a significant expansion of cells that retained CD133+CD34+ expression and their in vitro chemotactic ability to CXCL12. Time constraints did not permit the engrafting ability of these cells to be analysed in an in vivo HSC reconstitution assay that was initiated. However these studies will provide the basis to support future related research in this laboratory.
43
Lautenschlaeger, Franziska. "Cell compliance : cytoskeletal origin and importance for cellular function". Thesis, University of Cambridge, 2011. https://www.repository.cam.ac.uk/handle/1810/239393.
Testo completoAbstract (sommario):
Mechanical properties of cells, mainly defined by their cytoskeleton, are closely related to cell function and can be measured with a dual-beam laser trap (optical stretcher). Functional changes, which go hand in hand with changes of the cytoskeleton, also occur during differentiation of stem cells. This suggests monitoring differentiation by the changing compliance of the cells. During the course of my PhD I measured the compliance of three different types of stem cells before and after differentiation and was able to detect differences in some of the cell types. In order to relate rheological experiments to cell migration as a further example of functional change I investigated the migration behavior of cells that showed different compliance and found differences in migration. I was additionally able to show an altered migration behavior after I actively changed the mechanical behavior of one cell type using cytoskeletal drugs. These migration experiments have been carried out in 2D and 3D migration assays. Furthermore, the influence of the stiffness of the surrounding material on the migration behavior has been investigated. After relating functional changes to changes in compliance, I studied which mechanisms can be used to actually influence cell compliance and investigated the effect of cytoskeletal stabilizers or destabilizers as well as drugs acting on molecular motors. The effect of the surrounding temperature has been considered as well. Finally, I developed a new version of the optical stretcher measurement tool, which enables cell sorting and drug screening using a monolithic glass chip. With the results presented in this thesis I relate mechanical compliance to the cytoskeleton and specific cellular functions. I deliver insights how mechanical changes in cells can be used to identify and follow functional changes and how this knowledge can help to interfere with such functions, specifically in pathologies correlated to these functions. My modified optical stretcher would be developed to screen the effects of drugs on cell compliance and to sort cells with different mechanical properties. Such drug screening and cell sorting will offer diagnostic treatment options for various pathologies.
44
Dai, Meiou. "Regulation of TGFß signaling on tumor cell migration, invasion and stem cell activity in triple negative breast cancer". Thesis, McGill University, 2013. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=119559.
Testo completoAbstract (sommario):
Basal-like triple negative breast cancers (TNBCs) display poor prognostic features with larger tumor size, higher tumor grade, and an increased risk for lymph node and distant metastasis as well as tumor recurrence. Transforming growth factor beta (TGFβ) is a key regulator of the cellular processes by which breast cancer cells from the primary tumor metastasize to distant organs. However, the molecular mechanisms underlying TGFβ's pro-metastatic effects remain to be fully elucidated. Here, we investigated the role of TGFβ signaling pathway in regulating cell migration, invasion and cancer stem cell self-renewal capacity, which are the initial and critical steps in breast cancer metastasis. Our studies initially identified a novel function for the cell cycle regulator p21 and its binding partner acetyltransferase p/CAF as critical transcriptional regulators of TGFβ-induced TNBC cell migration and invasion in vitro as well as tumor invasiveness in vivo. As p21 can interact with different cyclin and CDK complexes, we investigated whether other cell cycle regulators are also involved in TGFβ-induced tumor progression. We found that TGFβ promotes physical interaction and nuclear co-localization between cyclin D1 and p21. The co-expression of cyclin D1 and p21 proteins promote tumor growth and locally invasive tumors. In addition, we found that TGFβ can activate cyclin D1/CDK4 complex to promote cancer stem cell activity and self-renewal capacity in TNBC. Together, we have defined p21, cyclin D1 and CDK4 as key downstream regulators of TGFβ tumor-promoting functions.Le cancer du sein triple-négatif (CSTN) de type basal démontre des signes cliniques caractéristiques d'un mauvais pronostique, tels qu'une taille et un grade plus élevés des tumeurs, un risque augmenté de développer des métastases lymphatiques et distantes, ainsi qu'un plus grand risque de récurrence de la maladie. Le TGFβ est un régulateur clé des procédés cellulaires par lesquels les cellules cancéreuses du cancer du sein se détachent de la tumeur primaire pour former des métastases aux organes distants. Cependant, les mécanismes moléculaires par lesquels le TGFβ accomplit son rôle pro-métastatique restent à être élucidés. Ici, nous investiguons le rôle du TGFβ dans la régulation de la migration cellulaire, l'invasion, et la capacité des cellules souches à se renouveler, qui sont les étapes initiales et critiques à la formation de métastases dans le cancer du sein. Notre étude a tout d'abord identifié une nouvelle fonction pour le régulateur de cycle cellulaire p21 et son partenaire associé, l'acetyltransférase pCAF, comme étant des régulateurs de transcription dont la présence est critique pour la migration et l'invasion cellulaire in vitro et l'invasion tumorale in vivo médiées par le TGFβ pour le CSNT. Le p21 pouvant interagir avec différents complexes de cycline et CDK, nous avons investigué si d'autres régulateurs du cycle cellulaire sont aussi impliqués dans la progression tumorale médiée par le TGFβ. Nous avons trouvé que le TGFβ promeut l'interaction physique et la co-localisation nucléaire entre la cycline D21 et p21. La co-expression de la cycline D1 et de p21 promeut la croissance tumorale et l'invasion locale des tumeurs. De plus, nous avons trouvé que le TGFβ peut activer le complexe cycline D1/CDK4 pour promouvoir l'activité des cellules souches cancéreuses, ainsi que leur capacité de renouvèlement dans le CSNT. Ces résultats nous ont permis de définir p21, la cycline D1, et CDK4, comme des régulateurs clés en aval du TGFβ dans ses fonctions pro-métastatiques
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Jiang, Lixian. "Interactions of Neurons, Astrocytes and Microglia with HUCB Cell Populations in Stroke Models: Migration, Neuroprotection and Inflammation". [Tampa, Fla] : University of South Florida, 2008. http://purl.fcla.edu/usf/dc/et/SFE0002552.
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Newman, Mary B. "Human umbilical cord blood cells migration to stroke cns tissue extracts and the potential cytokines and chemokines involved". [Tampa, Fla.] : University of South Florida, 2005. http://purl.fcla.edu/fcla/etd/SFE0001206.
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Bhaloo, Shirin Issa. "Vascular stem cell migration in response to Dkk3 in vascular diseases : the emergence of a novel chemokine-like protein". Thesis, King's College London (University of London), 2017. https://kclpure.kcl.ac.uk/portal/en/theses/vascular-stem-cell-migration-in-response-to-dkk3-in-vascular-diseases(17def3fe-c868-4b24-9187-5c470d7c13ae).html.
Testo completoAbstract (sommario):
Stem/Progenitor cells, such as Sca-1+ cells, are abundant in the vascular adventitia and they can differentiate into SMCs and ECs. These cells participate in the vascular wall remodeling observed in atherosclerosis, injury-induced neointimal hyperplasia and vein graft atherosclerosis. The detailed mechanisms of progenitor cell migration towards the intima have not been fully investigated. We hypothesize that Dkk3 plays an important role in resident Sca-1+ vascular progenitor cell migration. In this work, mouse vascular progenitor cells were isolated from the adventitia and sorted for the Sca-1 marker. Using transwell and wound healing assays, we showed that Dkk3 induced adventitia-derived Sca-1+ vascular progenitor cell (Sca-1+ APCs) migration in vitro. Additionally, the aortic ring assay demonstrated that Dkk3 was also able to induce Sca-1+ cell migration ex vivo. Analysis of the signaling pathways revealed that MAPK kinase signalling cascade, PI3K/AKT pathway and Rho-GTPases family of proteins were involved in the regulation of Dkk3-induced Sca-1+ progenitor cell migration. Our experiments also identified similarities in the migratory response of Sca-1+ cells to Dkk3 and Sdf-1α. Sdf-1α receptors are well established and they include CXCR4 and CXCR7. In contrast, the receptor for Dkk3 has not been identified yet. The current study aimed at identifying the receptor(s) involved in Dkk3-driven migration of Sca-1+ cells. Co-IP analysis and Affinity Binding assay revealed that Dkk3 binds to CXCR7. The downregulation of CXCR7 by SiRNA transfection reduced Dkk3-mediated Sca-1+ APC migration and the activation of the downstream signalling pathways. Overexpression of CXCR7, on the contrary, enhanced cell migration. In order to perform an exhaustive analysis of the potential binding partners of Dkk3 and identify additional receptors, we performed a Yeast Two Hybrid experiment. The results showed that integrin α5 (ITGα5) and integrin β1 (ITGβ1) interacted with Dkk3. Co-IP and Affinity Binding assays confirmed that Dkk3 bound to ITGα5 and ITGβ1. Furthermore, downregulation of these integrins by SiRNA transfection supressed the migration of Sca-1+ APCs triggered by Dkk3. Our work shows for the first time that Dkk3 acts as a chemokine-like protein able to induce the migration of resident Sca-1+ vascular progenitor cells. The pioneer identification of Dkk3 receptors and the elucidation of the signalling pathways involved in Sca-1+ APC migration could be of major interest for the development of novel drug-targeted therapies in vascular diseases.
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Elster, Jennifer Leith. "Quantification and Tracking of Transplanted Satellite Cells". Diss., The University of Arizona, 2009. http://hdl.handle.net/10150/195718.
Testo completoAbstract (sommario):
Satellite cells are adult stem cells that contribute to hypertrophy and repair in muscles. It is hypothesized that in muscular dystrophy, the satellite cells population is depleted at a very early age, due to repeated muscle damage and repair. Satellite cell transplantation is a potentially useful therapy for muscle diseases, but the lack of an efficient delivery system has hindered its application. The presented work focuses on two specific aims that address the need for more effective cell delivery methods for cell-based therapy. In Specific Aim 1 enhanced tissue culture techniques, such as heat stress, are used to increase cell survival in satellite cell transplantation studies. Also addressed within this specific aim are methods to label and evaluate performance using real-time PCR techniques.Although much work remains to enhancing the viability of in vitro expanded myoblasts derived from satellite cells, a second important hurdle is the systemic delivery of satellite cells to multiple sites (all muscles, in the case of muscular dystrophies). In vitro and in vivo experiments are being undertaken to explore the physiological role of cell signaling systems involved in directed migration and to determine if these chemokine and growth factors can be manipulated to enhance efficacy of cell-based therapies involving skeletal muscle satellite cells. Specific Aim 2 addresses migration of satellite cells to sites of injury and methods to track transplanted cells within the host. Presented here is the use of FAST SPECT II imaging of 111-Indium oxine radiolabeled satellite cells. The long lifetime of 111-indium oxine and the ability to quantify label using FAST SPECT imaging techniques make this technique ideal for in-vivo tracking of transplanted satellite cells for week long studies. Without in-vivo imaging techniques cell fate studies require sequential animal sacrifice with histological sectioning. This not only increases the number of animals used but also adds a significant inter-animal variability to their assessment. The determination of cell fate after transplantation will have a major impact on cell therapy for treatment of muscle disease as well as other stem cell therapies.
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Lindström, Henrik. "Migration to P4-Programmable Switches and Implementation of the Rapid Spanning Tree Protocol". Thesis, Linköpings universitet, Programvara och system, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-167509.
Testo completoAbstract (sommario):
P4 is a high-level language for programming the data plane of a network switch. These P4-programmable switches come with no pre-defined behavior or protocols, so it is entirely up to the loaded P4 program to define these. This allows the user to exclude any unwanted functionality and to create custom protocols. It also removes the dependence on the switch vendor in terms of both trust and addition of new features. This thesis looks at migration from traditional switches to P4-programmable ones. Since no behavior is included out-of-the-box in the P4 switches, a search is made for open-source P4 projects and the functionality they provide is evaluated. It is found that most link layer functionality can be achieved with them, with the exception being loop prevention by spanning tree protocols. Therefore, one of the projects is extended with an implementation of the Rapid Spanning Tree Protocol based on the IEEE 802.1D-2004 standard. Finally, partial migration of networks to P4 switches and to the Software Defined Networking (SDN) paradigm is studied based on a literature review. Four general approaches and specific architectures for these are found, and it is concluded that such a hybrid network can still benefit from P4 and having a centralized SDN controller.
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Salha, Sonia [Verfasser], e Lukas [Akademischer Betreuer] Prantl. "PDGF regulated migration of mesenchymal stem cells towards malignancy acts via the PI3K signaling pathway / Sonia Salha ; Betreuer: Lukas Prantl". Regensburg : Universitätsbibliothek Regensburg, 2019. http://d-nb.info/1201160669/34.
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