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Price, R. C. "Sparse matrix optimisation using automatic differentiation." Thesis, University of Hertfordshire, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.379908.
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Nyqvist, Jennifer. "Operational technology definition and differentiation : In the context of operational systems in Sweden." Thesis, Högskolan i Skövde, Institutionen för informationsteknologi, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-18752.
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ICS, short for Industrial Control Systems, can be a part of the electrical and water supplies among others, which are important instances for society. This all resides in the realm of Operational technology, abbreviation OT. Due to technological development, Information Technology i.e. IT is introduced and merged into the realm of industrial systems, because of society’s increasing dependencies on digital infrastructures and services.ICS and Supervisory Control and Data Acquisition (SCADA) systems are rather well known and reputable. In the realm of OT, there’s a range of different systems, and ICS itself encompasses a range of process automation technologies, such as SCADA systems and Distributed Control Systems (DCS) among others.This paper aims to try to define and differentiate a distinct boundary of systems without any connection to IT and can be considered purely OT, if they exist at all. This by conducting an interview with people working for governmental agencies with an eminent amount of experience in the realm of OT. What kind of systems are currently in operation today that don’t fit into the realm of ICS, do they exist at all and how do they work?The definition and differentiation of OT may indicate a subset of systems and components, and terminologies of systems in the OT-realm are misused, indicating a lack of insight in this realm of industrial systems.
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Lochter, André. "Control of neuronal differentiation by extracellular matrix constituents /." [S.l.] : [s.n.], 1993. http://e-collection.ethbib.ethz.ch/show?type=diss&nr=10325.
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Richardson, Lucy Elizabeth. "Extracellular matrix cues for mesenchymal stem cell differentiation." Thesis, Royal Veterinary College (University of London), 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.444369.
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Kurth, Ina. "Hematopoietic Stem Cell Differentiation inside Extracellular Matrix functionalized Microcavities." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2011. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-68614.
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The bone marrow (BM) niche provides hematopoietic stem (HSC) and progenitor cells with many exogenous cues that tightly regulate homeostasis. These cues orchestrate cellular decisions, which are difficult to dissect and analyze in vivo. This thesis introduces a novel in vitro platform that permits systematic studies of BM-relevant factors that regulate homeostasis. Specifically, the role of 3D patterned adhesion ligands and soluble cytokines were studied in a combinatorial fashion. Analysis of human HSC differentiation and proliferation at both population and single cell level showed synergistic and antagonistic effects of adhesion- and cytokine-related signals. Those effects were dependent on the cytokine concentration and the distribution and number of adhesion ligands. The aim of this thesis was to model the in vivo bone marrow with its porous 3D structure and different sized niche compartments using a microcavity culture carrier. The developed culture system presented extracellular matrix (ECM) adhesion ligands to the HSCs in various defined dimensions ranging from single- to multi-cell capacity. The 3D open well geometry of the microcavity carriers also allowed HSCs to freely explore different scenarios including homing, migration, adhesion, or suspension. Furthermore, the developed setup offered straightforward accessibility to analytical methods like cytometry and quantitative microscopy. Single cell analysis of adherent HSCs showed decreased DNA synthesis and higher levels of stem cell marker expression within single cell microcavities under low cytokine conditions . This effect was reflected in a decline of proliferation and differentiation with decreasing microcavity size. When the cytokine concentration was increased2 beyond physiological levels the inhibitory effect on proliferation and differentiation due to single-cell-microcavity adherence was diminished. This result highlighted the fine balance between adhesion related and soluble cues regulating HSC fate. Within small microcavities more adhesion related receptors were engaged due to the 3D character of the culture carrier compared to multi-cell wells or conventional 2D cell culture plates. This study demonstrated that adhesion-related signal activation leads to reduced proliferation and differentiation. This geometry-based effect could be reversed by increased cytokine supplementation in the culture media. For plane substrates, HSCs attachment to fibronectin or heparin initiated early cell cycle entry compared to non-adherent cells during the initial 24h. Cytokine supplemented media favored integrin activation that induced fast adhesion, ultimately leading to early cell cycle activation. However, after prolonged cell culture the system balanced itself with a lower cycling rate of adherent versus non-adherent HSCs. Furthermore, HSCs within the 3-dimensionality of the microcavities cycled less than 2D adherent cells. These findings additionally supported the above stated idea of limited HSC proliferation as a consequence of more adhesion-related signals overwriting cytokine driven expansion. To complement the various in vitro studies, an in vivo repopulation study was performed. Cultured HSCs derived from single cell microcavities outperformed freshly isolated HSCs in a competitive repopulation assay, indicating that carefully engineered substrates are capable of preserving stem cell potential. Overall the reported findings provide a promising in vitro culture strategy that allows the stem cell field to gain a better understanding of the impact of distinct exogenous signals on human HSCs, which discloses new concepts for the wide scientific community working towards tissue engineering and regenerative medicine<br>Die Homöostase der Hämatopoietischen Stamm- und Vorläuferzellen (HSC) in der Knochenmark Nische wird von einer Vielzahl exogener Faktoren gezielt reguliert. Diese Faktoren orchestrieren intrazelluläre Vorgänge, deren in vivo Analyse kompliziert ist. Die vorliegende These widmet sich einem neuen biotechnologischen Ansatz, der systematische Studien von Knochenmark-relevanten Faktoren ermöglicht. Im Speziellen wurde die Rolle 3D-präsentierter Zell Adhäsionsliganden in Kombination mit verschiedenen Konzentrationen löslicher Zytokine untersucht. Die Auswertung der Proliferation und Differenzierung von humanen HSC auf Einzelzell- und Populationsebene offenbarte die synergistischen und antagonistischen Effekte von Adhäsions- und Zytokinsignalen in ihrer Abhängigkeit von der Verteilung und der Anzahl von Adhäsionsliganden sowie der Zytokinkonzentration. Um die poröse Struktur des Knochenmarks in vivo-ähnlich darzustellen, wurde eine Zellkultur Plattform mit Mikrokavitäten verschiedenster Dimensionen von Multi- bis Einzelzellgröße entwickelt und mit Molekülen der extrazellulären Matrix beschichtet. Die Vorteile dieser Plattform liegen in der offenen 3D-Geometrie dieses mikrokavitäten Kultursystems, die den Zellen ermöglichte verschiedene Wachstumsbedingungen bezüglich Homing, Migration, Adhäsion oder Suspension frei zu erkunden. Das leicht zugängliche Setup eignete sich zudem hervorragend für die zytometrische Analyse der Zellen oder die quantitative Mikroskopie. Die Einzelzellanalyse adhärenter HSC ergab eine Reduktion von DNA Synthese und eine höhere Expression von Stammzelloberflächenfaktoren innerhalb der Einzelzell-Mikrokavitäten bei niedrigen Zytokinkonzentrationen . Dieser Effekt spiegelte sich auch auf Populationsebene in verminderter Proliferation und Differenzierung mit abnehmender Größe der Mikrokavitäten wider. Wurde die Zytokinkonzentration jedoch weit über physiologische Bedingungen erhöht, verminderte sich der Effekt (reduzierte DNA Synthese und höhere Stammzellfaktorexpression) beschrieben für die Einzelzellmikrokavitäten. Dieses Ergebnis verdeutlicht die empfindliche intrazelluläre Balance, vermittelt durch Adhäsionsignale und löslichen Faktoren, die das Verhalten von HSCs regulieren. Aufgrund des 3D-Charakters des Zellkulturträgers wurden innerhalb kleiner Mikrokavitäten mehr Adhäsionsrezeptoren ringsum die Zelle aktiviert. Dieser Vorteil gegenüber den Multizellkavitäten oder der herkömmlichen 2D–Zellkultur ermöglichte eine hohe Anzahl adhäsionsvermittelter Signale mit entsprechend höherer Proliferations-inhibitorischer Wirkung. Je höher die Konzentration der Zytokine war, desto stärker erfolgte die Stimulation der Proliferation und Differenzierung. Auf 2D Substraten, initiierte Adhäsion zu Fibronektin und Heparin innerhalb der ersten 24h einen frühen Zell-Zyklus-Start im Gegensatz zu nicht adhärenten Zellen. Die Zytokine im Zellmedium förderten die Integrin Aktivierung, was zu einer schnellen Zelladhäsion führte. Die Adhäsionsrezeptoren wiederum kooperieren mit Zytokinrezeptoren im Zellinneren und begünstigten damit einen zeitigeren Zell-Zyklus- Start. Allerdings stellte sich danach ein Gleichgewicht im Kultursystem ein, wobei weniger adhärente Zellen als nicht-adhärente Zellen den Zellzyklus durchliefen. Des Weiteren war die Zellzyklusrate innerhalb von 3D Mikrokavitäten niedriger verglichen mit herkömmlichen 2D Substraten. Diese Ergebnisse bestätigen ferner obenstehende These, dass Zytokin-induzierte Zellexpansion durch erhöhte Zelladhäsions-vermittelte Signale überschrieben wird. Um die in vitro Studien zu komplettieren wurde ein in vivo Repopulationsversuch durchgeführt. HSC kultiviert auf Einzel-Zell-Mikrokavitäten übertrafen frisch isolierte Konkurrenz-Zellen in einem kompetitiven Repopulationsversuch. Dieses erste Ergebnis zeigt, dass sich der Zellgröße entsprechende Biomaterialien für die erfolgreiche Stammzell-Kultur eignen. Die Ergebnisse dieser Arbeit bieten eine vielversprechende in vitro Zellkulturstrategie, die ein besseres Verständnis der Einflüsse von exogenen Signalen auf HSC erlaubt und damit eine Grundlage für neue Erkenntnisse in Richtung erfolgreicheres Tissue Engineering und klinische Anwendungen im Bereich der regenerativen Medizin bildet
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Al-Jallad, Hadil. "Role of transglutaminase enzymes in osteoblast differentiation and matrix deposition." Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=106326.
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Bone formation is an osteoblast-mediated process that is controlled by systemic factors such as hormones, growth factors and local cues that arise from the extracellular matrix (ECM). Bone ECM is elaborated by osteoblasts and therefore they can control their own activity. The ultimate goal of bone matrix formation is to elaborate an extracellular network, consisting mainly of fibronectin and collagen type I, that is capable of mineralizing and forming a strong tissue with appropriate tensile and elastic properties. This thesis describes studies that link transglutaminases (TGs), the protein cross-linking enzymes to type I collagen matrix deposition, osteoblast differentiation and bone formation. Findings here show that MC3T3-E1 osteoblasts require TG-activity for differentiation and proper production of collagenous matrices. We also show that osteoblasts produce two transglutaminase enzymes, transglutaminase 2 (TG2) and Factor XIIIA (FXIIIA), which are both expressed during osteoblast differentiation. The work further defines the roles of the two TGs in osteoblasts and shows that FXIIIA is the main TG-enzyme with transamidating activity in osteoblasts' ECM. Production of FXIIIA is induced during osteoblast differentiation and is externalized to the cell surface, then secreted to the ECM. TG2 was mainly found on the cell surface of osteoblasts with no transamidating activity; however, it is co-localized with FXIIIA on the cell surface. Studies conducted with chemical inhibitors, TG-substrates and activity probes suggest that TG-activity is required for osteoblast differentiation at three different levels. First, by positively affecting microtubule dynamics, delivery and fusion of secretory vesicles carrying cellular collagen type I to the plasma membrane. Second, by promoting fibronectin matrix deposition and collagen type I secretion. And third, by stabilizing the interaction between fibronectin and collagen type I in the ECM. Furthermore, we demonstrated that tubulin and fibronectin are candidate substrates for FXIIIA in osteoblasts. In summary, our studies are the first to describe FXIIIA transglutaminase expression in osteoblasts in vitro and in vivo, and first to link it to collagen secretion and osteoblast differentiation. Furthermore, these studies were the first to suggest a role for cellular FXIIIA in microtubule dynamics. We conclude that transglutaminase activity arising from FXIIIA can regulate osteoblast differentiation affecting extracellular matrix deposition.<br>La formation et le développement de l'os est un processus complexe dirigé par les ostéoblastes. Contrôlés par des hormones systémiques, des cytokines et d'autres facteurs locaux, les ostéoblastes sécrètent et assemblent la matrice extracellulaire (MEC) des tissus osseux. L'aboutissement de ce processus sera la génération d'un réseau extracellulaire constitué notamment de la fibronectine et du collagene de type I qui va se minéraliser en formant le tissu dur de l'os avec d'excellent propriétés mécaniques. Cette thèse présente des études liées aux transglutaminases (TGs) – une classe des enzymes responsables de la polymérisation (cross-linking) des protéines et d'autres composée biomacromoléculaires - en relation avec le collagène de type I secrété pendant l'élaboration de la MEC, la différentiation des ostéoblastes et l'élaboration du tissu osseux. Les principaux résultats de ces études portent sur l'observation que l'activité polymérisante de la TG est un facteur crucial pour la différentiation des cellules ostéoblastiques MC3T3-E1 et pour la production normale de la matrice collagénique. Un résultat essentiel de la présente recherche porte sur la découverte que les ostéoblastes synthétisent deux types d'enzymes TG, i.e. la transglutaminase 2 (TG2) et le facteur XIIIA (FXIIIA), qui sont tous les deux secrétés pendant la différentiation des ostéoblastes. Les résultats suivants éclaircirent les rôles des deux enzymes TG (TG2 et FXIIIA) dans l'activité des ostéoblastes en montrant que c'est le FXIIIA qui est l'enzyme TG dominante avec une activité de transamidation importante dans la MEC des ostéoblastes. FXIIIA est produit pendant la différentiation des ostéoblastes en s'externalisant vers la surface des cellules pour être par la suite sécrété dans la MEC. L'enzyme TG2 a été localisé seulement à la surface des cellules osteoblastiques. Même si le TG2 a été trouvé colocalisé avec le FXIIIA à la surface des cellules, aucune activité de transamidation n'est identifiée pour le TG2. Des études comportant des inhibiteurs chimiques, de substrats TG et de sondes d'activité TG suggèrent que l'activité TG est nécessaire pour la différentiation des ostéoblastes sur trois plans distincts, à savoir : (i) par une action bénéfique sur la dynamique des microtubules, l'acheminement et la fusion des vésicules sécrétoires qui transportent le collagène I cellulaire vers la membrane plasmatique; (ii) par l'accélération du dépôt de la matrice de fibronectine et la sécrétion du collagène de type I; (iii) par la stabilisation de l'interaction de la fibronectine avec le collagène I dans la MEC. De plus, nous avons démontré que la tubuline and la fibronectine ce sont de candidats substrat pour le facteur FXIIIA dans les ostéoblastes. En résumé, notre recherche décrit pour la première fois l'expression de l'enzyme transglutaminase FXIIIA dans les ostéoblastes, tant in vitro qu'in vivo, en corrélant l'expression du FXIIIA à la sécrétion et la différentiation des ostéoblastes. De plus, notre étude est la première en attribuant un rôle au facteur FXIIIA relative à la dynamique des microtubules. On conclut de notre étude que l'activité transglutaminase du facteur FXIIIA exerce une influence décisive dans les processus de différentiation des ostéoblastes avec un effet régulateur crucial à la sécrétion et au dépôt de la matrice extracellulaire.
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Amin, H. D. "Effects of enamel matrix derivative components on PDL cell differentiation." Thesis, University College London (University of London), 2011. http://discovery.ucl.ac.uk/1322447/.
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Previous studies have reported that the adult periodontal ligament (PDL) may contain progenitor/stem cells that function as precursors for periodontal tissue regeneration, although the ability of this population to differentiate into the multiple lineages present in the PDL is not yet certain. In addition, although Enamel Matrix Derivative (EMD; Emdogain®), derived from the enamel matrix of developing teeth) has been used extensively to help re-build new periodontal tissue, its effect on bone regeneration remains inconclusive and its effect on PDL blood vessels and nerve cell development not yet known, because it comprises a heterogeneous mixture of proteins. EMD has recently been separated into two main fractions: Fraction C, containing proteins < 6 kDa (mainly the tyrosine-rich amelogenin peptide TRAP); and Fraction A, containing proteins > 6 KDa (including the full-length amelogenin, sheathlins and a leucine-rich amelogenin peptide LRAP). The present study examined the effects of EMD Fractions on multi-lineage differentiation pathays of PDL cells in vitro. The results of the present study have shown that that Fraction C and Fraction A differentially regulate multilineage specification of PDL cells. Thus, Fraction C was found to up-regulate chondrogenic, vasculogenic, angiogenic, neurogenic and gliogenic genes and ‘terminal’ differentiation, whereas Fraction A was found to stimulate osteogenic genes and terminal osteogenic differentiation in vitro; both fractions suppressed adipogenesis. Moreover, the TRAP and LRAP peptides of Fraction C and Fraction A, respectively, were found to be at least partly responsible for the differential activities of these two fractions. In addition, at least some components in these EMD Fractions bound to and were internalized into PDL cells, most probably by receptor-mediated endocytosis. These findings thus demonstrate that the PDL contains cells with multi-lineage differentiation potential and that the components of EMD have differential effects on the diverse activities on the heterogeneous cells present in the PDL.
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Delaine-Smith, Robin M. "Mechanical and physical guidance of osteogenic differentiation and matrix production." Thesis, University of Sheffield, 2013. http://etheses.whiterose.ac.uk/3691/.
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Summary Tissue engineering and regenerative medicine strategies until now have mostly relied on static culture using chemical stimulation to induce cell differentiation. However, these strategies neglect the dynamic environment in which cells reside in the body where they are surrounded by a chemically and physically well-defined threedimensional (3D) topography. Not only does this environment control cellular differentiation, but its structure also determines the mechanical function of that tissue. Alongside physical cues, external mechanical forces play an essential role in the homeostasis of many tissues, particularly bone. In order to develop tissue engineered constructs that are suitable for implantation, it may be important to incorporate these essential cues into pre-culture methods and in order to do this, a better understanding of the cellular responses is required. The main aim of this research was to understand how physical and mechanical cues affect cell behaviour, differentiation and matrix production, with particular emphasis on osteogenesis and collagen organisation. In order to achieve this, electrospun scaffolds were fabricated with controllable fibre orientation for studies involving fibroblast matrix organisation, and the affect on the differentiation of osteoprogenitor cells. Short bouts of tensile loading were conducted using a previously established bioreactor model for conditioning collagen-producing cells. A simple rocking platform method for subjecting cells to fluid-flow was also investigated for its potential to enhance osteogenesis and collagen organisation. This system was further used to study the role of the primary cilium for the mechanotransduction of bone cells. The overall goal was to understand how to manipulate cell differentiation and matrix production in order to develop a more suitable construct with correct tissue structure in a rapid manner. Monitoring of the major structural matrix protein collagen was achieved using the minimally-invasive technique of second harmonic generation, which was optimised. Electrospun scaffolds with a random architecture caused cells to deposit matrix in a similar random manner, however highly aligned scaffolds caused deposited collagen to orientate in the fibre direction giving superior tensile properties. Further to this, random fibres appeared to be more favourable for the differentiation of osteoprogenitor cells than highly aligned substrates. 9 Short bouts of tensile stimulation of collagen producing cells on 3D substrates caused an increase in collagen deposition. Another stimulation method, a simple rocking platform, created oscillatory fluid shear stress (FSS) suitable for stimulation of osteogenic cells and enhanced collagen organisation. Further to this, human dermal fibroblasts could be induced to form a mineralised matrix when cultured in osteogenic media, which was further enhanced with FSS. It was also demonstrated that this simple rocking system could be used to test a wide variety of loading parameters. Finally, rocking was used to examine the role of the primary cilium in the load-induced mineral deposition response of bone cells. When mature bone cells were subjected to FSS, primary cilia shortened in length and removal of primary cilia resulted in loss of the load-induced matrix response suggesting that primary cilia are mechanosensors in bone cells.
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Helwig, Bryan Glen. "Neuronal differentiation of stem cells derived from human umbilical cord matrix /." Search for this dissertation online, 2003. http://wwwlib.umi.com/cr/ksu/main.
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Xu, Yanyi. "Matrix Property-Controlled Stem Cell Differentiation for Cardiac and Skeletal Tissue Regeneration." The Ohio State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=osu1440161684.
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Ramage, Samuel. "The Role of Secreted Phosphoprotein-24 in Osteoblast Differentiation and Matrix Mineralization." VCU Scholars Compass, 2007. http://scholarscompass.vcu.edu/etd/1604.
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Secreted Phosphoprotein-24 (Spp24) was initially isolated and characterized as a component of bovine cortical bone matrix. Subsequent characterization has shown it is multiply phosphorylated and homologous to cystatin and TGF-β receptor type II. Spp24 is a minor component of the serum fetuin mineral complex that binds calcium-phosphate minerals and prevents their deposition. The TGF-β receptor homology domain binds BMP-2 weakly in vitro and enhances BMP-2’s osteogenic effects in vivo. The ability of Spp24 to affect BMP activity suggests an important role for Spp24 as a native, bioactive componentof bone that regulates bone development.
Spp24 was highly up-regulated in rat cortical kidneys following a low calcium diet regime. Tissue distribution of both Spp24 protein and RNA showed that while Spp24 accumulates in bone, a majority is produced at distant sites, namely the liver and kidney. Additionally, Spp24 was present in more tissues than previously believed. Spp24 migrates to a number of different molecular weights, suggesting multiple, alternative posttranslational modifications may generate subtly different forms of the protein. Theexpression of Spp24 in the kidney may be regulated to counteract changes in serum mineral levels. Additionally, homology in the Spp24 sequence suggests that it, like other bone and dentine matrix proteins, may interact with mineral as an important influencer of mineral calcification.
Utilizing microarray analysis of primary bone marrow-derived mesenchymal stem cells transduced with Spp24 and control viruses we examined changes elicited by the overexpression of Spp24. A change in overall morphology was observed for cellstransduced with the Spp24 similar to changes described in cells undergoing osteoblasticdifferentiation. Nodule formation was also seen in the Spp24 transduced cells. Microarray results showed key markers of osteoblast differentiation, CBFA1/RUNX2 and osterix(OSX), were not up-regulated although there were distinguishable changes in the gene expression profile of mesenchymal stem cells. The cells appeared to be blocked from differentiation into a number of mesenchymal lineages: adipocytes, myocytes andchondrocytes. The changes appeared to prime cells for signals that activate osteoblastdifferentiation by blocking other pathways and altering internal signaling response pathways to those signals.
This document was created in Microsoft Word 2003.
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Ramage, Samuel Cowan. "The role of secreted phosphoprotein-24 in osteoblast differentiation and matrix mineralization /." Available online after August 19, 2013, 2007. http://hdl.handle.net/10156/2291.
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D'Arrigo, Corrado. "Adhesion of B16 malignant melanoma cells to the endothelium and to subendothelia matrix components." Thesis, University of St Andrews, 1991. http://hdl.handle.net/10023/14063.
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During the haematogenous spread of tumours, the metastasizing cells must arrest within the blood vessels of the organs they colonize. There is still much debate upon the mechanism of such arrest, whether it is due to mechanical trapping or, more specifically, to adhesion of the tumour cells to the blood vessel wall. This work demonstrates that tumour cells are capable of adhering to blood vessel wall components. According to the hypothesis of specific adhesion, it is thought that metastasizing tumour cells would only come into contact with the vessel wall for a very short time and therefore their adhesion to the vessel wall must be extremely rapid. It has been shown in the past that tumour cells can adhere rapidly to components of the blood vessel wall such as exposed sub-endothelial matrix. Adhesion to endothelial cells was believed to occur at a much slower rate and therefore the involvement of the endothelium during the arrest phase of the metastatic process was thought to be marginal. The experiments carried out during this study show that, in vitro, tumour cells do adhere to the endothelium at a rate comparable to that for isolated components of the sub-endothelial matrix. Furthermore, this work provides some evidence that the molecular basis for such rapid adhesion to the endothelium may be different from the ones involved in the adhesion to known components of the sub-endothelial matrix.
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Caramelo, Inês Isabel Nunes. "Mechanomodulation of chondrogenic differentiation of msesenchymal stem cells." Master's thesis, Universidade de Aveiro, 2017. http://hdl.handle.net/10773/22537.
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Mestrado em Bioquímica - Métodos Biomoleculares<br>A cartilagem hialina, cujas células especializadas são os condrócitos, encontra-se maioritariamente presente nas articulações. A degeneração deste tecido está associada a envelhecimento e a diversas doenças como artrite reumatóide e osteoartrite. Recentemente, tem sido investigada a possibilidade de desenvolver terapias celulares para o tratamento destas patologias, utilizando células estaminais mesenquimais (MSCs). As MSCs têm capacidade para se diferenciar em várias linhagens, incluindo condrócitos, apresentando-se como um dos mais promissores tipos celulares em medicina regenerativa. Nos últimos anos as vias de sinalização iniciadas pelos estímulos mecânicos do meio envolvente – mecanotransdução - tem sido alvo de estudo. Apesar dos mecanismos de diferenciação condrogénica não serem completamente conhecidos, tem-se tornado evidente que a mecanotransdução desempenha um papel crucial neste processo. Foi recentemente demonstrado que as MSCs têm “memória mecânica” e que, se cultivadas por mais de 10 dias num substrato rígido perdem a multipotência. Vários estudos utilizando células primárias ou MSCs apontam a rigidez ótima para diferenciação condrogénica deste 1 kPa até 320 MPa, dependendo do tipo de células e plataforma utilizados. Este estudo propôs-se então a clarificar qual a rigidez ótima para diferenciação condrogénica de MSCs. No presente estudo, foram preparados vários substratos de PDMS e caracterizados por reologia, apresentando módulos de Young que variam entre 21 kPa e 0.9 kPa. A diminuição da área nuclear nos substratos menos rígidos permitiu validar que estes substratos são capazes de induzir um estímulo mecânico. Somente células de baixa passagem foram induzidas a diferenciar diminuir o impacto da memória mecânica. A coloração de Safranin O (SO) permitiu evidenciar que a formação de aglomerados celulares – típica da condrogénese – é favorecida pelo substrato de 1 kPa. Recorrendo à fluorescência deste corante, foi possível estabelecer um método semi-quantitativo para avaliar diferenciação condrogénica de MSCs. Este ensaio indica que o substrato de 1 kPa potencia a diferenciação condrogénica de MSCs. Apesar dos resultados de SO requererem uma validação mais exaustiva por RT-PCR, os resultados preliminares apontam o que a rigidez ótima para diferenciação condrogénica de MSCs é de 1 kPa<br>Hyaline cartilage is composed by specialized cells named chondrocytes. It is mainly present on joints. Its degeneration is associated not only with ageing, but also with diseases like osteoarthritis and rheumatoid arthritis. Cell therapy is an emerging concept for these diseases. Mesenchymal stem cells (MSCs) can differentiate into various cell lineages, including chondrocytes. Recent studies indicate the significance of how cells are capable of sensing mechanical stimuli and initiate signaling cascades – mechanotransduction. Although the mechanisms are not totally understood, it is known that mechanotransduction plays a significant role during chondrogenesis. “Mechanical memory” is an emerging concept: it has been demonstrated that cells lose their multipotency if cultured on stiff substrates for more than 10 days. Distinct studies using primary cells or MSCs indicate that optimal matrix stiffness for chondrogenic differentiation is between 1 kPa and 320 MPa, depending on cell type and platform used. On the present study, we aimed to elucidate the optimal stiffness for chondrogenic differentiation of MSCs. Various PDMS substrates were produced and characterized by rheology, presenting Young’s modulus between 21 kPa and 0.9 kPa. We verified a decreasing tendency on the nucleus area along with substrate softening, suggesting that MSCs were responding to substrate stiffness. To reduce the influence of “mechanical memory”, only naïve cells were induced to differentiate. Safranin O (SO) staining revealed that 1 kPa substrate favored cell agglomeration, typical of chondrogenesis. Using fluorescence of this dye, we established a semi-quantitative assay to evaluate chondrogenic differentiation of MSCs. This assay suggests that 1 kPa substrate potentiates chondrogenic differentiation of MSCs. Despite SO assay results need further validation by RT-PCR, preliminary data indicates 1 kPa as the optimal stiffness for chondrogenic differentiation.
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McGuire, Vincent Michael. "Assembly and function of the PsB multiprotein complex during spore differentiation in Dictyostelium discoideum /." free to MU campus, to others for purchase, 1996. http://wwwlib.umi.com/cr/mo/fullcit?p9737858.
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Hewman, Rachel Esther. "The role of the extracellular matrix in human embryonic stem cell renewal vs differentiation." Thesis, University of Oxford, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.504297.
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Zou, Huiru. "The effect of enamel matrix protein on the odotogenic differentiation of dental pulp stem cells." Thesis, University of Leeds, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.536087.
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Soller, Eric C. "In vitro pharmacological inhibition of myofibroblast differentiation and force generation in a collagen-GAG matrix." Thesis, Massachusetts Institute of Technology, 2005. http://hdl.handle.net/1721.1/32343.
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Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2005.<br>Includes bibliographical references (leaves 35-39).<br>Induced regeneration studies from three organs in the adult mammal (skin, peripheral nerves, and the conjunctiva) suggest an antagonistic relationship between myofibroblast-mediated contraction of wounds and induced regeneration. In each instance of induced regeneration, contraction blocking was accomplished using regeneration templates, or scaffolds of highly specific structural and chemical properties that mainly control the environment or the density of contractile cells (myofibroblasts). In addition to scaffolds, diffusible factors could be used to inhibit specific components of the intracellular pathway in an effort to further evaluate the relationship between contraction and induced regeneration. The crucial role that Rho- associated coiled-coil forming protein serine/threonine kinase (ROCK) seems to play in cell-mediated contraction and cytoskeletal remodeling behavior of fibroblasts make it an attractive target for pharmacological inhibition. A preliminary in vitro study was conducted to evaluate the effect of Y-27632, a specific pharmacological inhibitor of ROCK, on the contraction of highly porous, three-dimensional type I collagen- glycosaminoglycan (CG) matrices over time by attached NR6WT fibroblasts treated with TGF-[beta]1, a known upregulator of both fibroblast contraction and expression of the contractile filament [alpha]-smooth muscle actin ([alpha]-SMA), a hallmark of the myofibroblast phenotype. NR6WT fibroblasts were seeded into free-floating cylindrical CG matrices (8 mm in diameter, n=6) and treated with serum-containing media supplemented with TGF-[beta]1 (3 ng/ml) or both TGF-[beta]1 (3 ng/ml) and Y--27632 (10 [mu]M) for 12 days.<br>(cont.) Control cells (untreated) were cultured as well as unseeded matrix controls. The diameter reduction of matrices was determined daily by visual comparison to circles of known diameter (...). Contraction was calculated as the change in matrix diameter from the day 0 value divided by the day 0 diameter and is a measure of radial strain in the substrate. Cell-mediated contraction (CMC) was determined by subtracting the contraction of the unseeded matrices from the contraction of the seeded matrices. The average number of attached fibroblasts per matrix for each experimental group was determined at the end of the 12 day contraction experiment. At a dosage of 10 [mu]M, Y-27632 significantly attenuated TGF-[beta]1-stimulated cell-mediated contraction of free-floating CG matrices by NR6WT fibroblasts. While Y-27632 treatment also decreased the cellular content of the matrices compared to control cells, the relative magnitudes of cell-mediated contraction (C(MC) normalized o the attached number of fibroblasts indicate a statistically significant difference between mean values for TGF-[beta]1 treated cells and cells treated with both TGF-[beta]1 and Y-27632 (p<0.001). The data suggest that cellular de-adhesion alone does not account for the inhibitory effect of Y-27632 on TGF-[beta]1 stimulated cell-mediated contraction of CG matrices. A likely explanation is that the inhibitor is blocking the ability of fibroblasts to express an agonist-induced contractile phenotype and instead encouraging the development of a more migratory one.<br>(cont.) The observed effect of the inhibitor on contraction could have been through inhibition of the contractile filament [alpha]-SMA, although expression of this protein was not assayed in this study. The demonstrated ability of Y-27632 to inhibit TGF-[beta]l1-stimulated force generation support its use in a future in vivo study that would evaluate the relationship between contraction blocking using pharmacological inhibitors and induced regeneration in a peripheral nerve wound model.<br>by Eric C. Soller.<br>S.M.
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Ito, Akira. "Culture temperature affects redifferentiation and cartilaginous extracellular matrix formation in dedifferentiated human chondrocytes." 京都大学 (Kyoto University), 2015. http://hdl.handle.net/2433/199220.
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Villaggio, Giusy. "Relationship between extracellular matrix (ECM) components and mineralization in bone marrow stromal cells." Doctoral thesis, Università di Catania, 2014. http://hdl.handle.net/10761/1492.
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The relations between cells and extracellular matrix seem to orchestrate tissue organization by regulating cell functions during fetal development and throughout normal adult life. Thus, focusing on the innate ability of the native ECM to better modulate cell behavior, the coating of synthetic biomaterials with cell-derived decellularized extracellular matrices is a promising approach to confer bioactivity to inert materials and direct the fate of host or transplanted cells in tissue engineering applications.
This study aims to better understand ECM influence on human bone marrow stem cells and its role during the induction of an osteogenic phenotype. For this purpose decellularized matrices were prepared and examined for viability, morphology, adhesion, ALP content, mineralization and gene expression.
Extracellular matrix coatings were able to delay, unlike uncoated surfaces, cell spontaneous differentiation, underlying its role in the preservation of cell stemness. Furthermore, the combination of free cell ECM with osteogenic medium resulted in a strong effect on cell differentiation.
In conclusion, the ECM provides an ideal environment that promote cell adhesion and proliferation creating an ideal setting for the large-scale expansion of MSCs. In addition, it could enhance, in the presence of osteogenic factors, the cells differentiative ability providing the basis for an easier tissue-specific fate control of MSCs for therapeutic applications.
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Farrell, Kurt W. "Role of Matrix Microenviroment on Neural Stem Cell Phenotype and Differentiation under Healthy and Inflammatory Conditions." Cleveland State University / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=csu1462009482.
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Vogel, Sarah, Simon Arnoldini, Stephanie Möller, Ute Hempel, and Matthias Schnabelrauch. "Sulfated hyaluronan alters fibronectin matrix assembly and promotes osteogenic differentiation of human bone marrow stromal cells." Nature Publishing Group, 2016. https://tud.qucosa.de/id/qucosa%3A29174.
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Extracellular matrix (ECM) composition and structural integrity is one of many factors that influence cellular differentiation. Fibronectin (FN) which is in many tissues the most abundant ECM protein forms a unique fibrillary network. FN homes several binding sites for sulfated glycosaminoglycans (sGAG), such as heparin (Hep), which was previously shown to influence FN conformation and protein binding. Synthetically sulfated hyaluronan derivatives (sHA) can serve as model molecules with a well characterized sulfation pattern to study sGAG-FN interaction. Here is shown that the low-sulfated sHA (sHA1) interacts with FN and influences fibril assembly. The interaction of FN fibrils with sHA1 and Hep, but not with non-sulfated HA was visualized by immunofluorescent co-staining. FRET analysis of FN confirmed the presence of more extended fibrils in human bone marrow stromal cells (hBMSC)-derived ECM in response to sHA1 and Hep. Although both sHA1 and Hep affected FN conformation, exclusively sHA1 increased FN protein level and led to thinner fibrils. Further, only sHA1 had a pro-osteogenic effect and enhanced the activity of tissue non-specific alkaline phosphatase. We hypothesize that the sHA1-triggered change in FN assembly influences the entire ECM network and could be the underlying mechanism for the pro-osteogenic effect of sHA1 on hBMSC.
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Vogel, Sarah, Simon Arnoldini, Stephanie Möller, Ute Hempel, and Matthias Schnabelrauch. "Sulfated hyaluronan alters fibronectin matrix assembly and promotes osteogenic differentiation of human bone marrow stromal cells." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2017. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-221028.
Full textAbstract:
Extracellular matrix (ECM) composition and structural integrity is one of many factors that influence cellular differentiation. Fibronectin (FN) which is in many tissues the most abundant ECM protein forms a unique fibrillary network. FN homes several binding sites for sulfated glycosaminoglycans (sGAG), such as heparin (Hep), which was previously shown to influence FN conformation and protein binding. Synthetically sulfated hyaluronan derivatives (sHA) can serve as model molecules with a well characterized sulfation pattern to study sGAG-FN interaction. Here is shown that the low-sulfated sHA (sHA1) interacts with FN and influences fibril assembly. The interaction of FN fibrils with sHA1 and Hep, but not with non-sulfated HA was visualized by immunofluorescent co-staining. FRET analysis of FN confirmed the presence of more extended fibrils in human bone marrow stromal cells (hBMSC)-derived ECM in response to sHA1 and Hep. Although both sHA1 and Hep affected FN conformation, exclusively sHA1 increased FN protein level and led to thinner fibrils. Further, only sHA1 had a pro-osteogenic effect and enhanced the activity of tissue non-specific alkaline phosphatase. We hypothesize that the sHA1-triggered change in FN assembly influences the entire ECM network and could be the underlying mechanism for the pro-osteogenic effect of sHA1 on hBMSC.
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Kuroda, Mito. "Mechanism of the ECM stiffness-dependent differentiation of mesenchymal stem cells." Kyoto University, 2018. http://hdl.handle.net/2433/232360.
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Kyoto University (京都大学)<br>0048<br>新制・課程博士<br>博士(農学)<br>甲第21159号<br>農博第2285号<br>新制||農||1060(附属図書館)<br>学位論文||H30||N5133(農学部図書室)<br>京都大学大学院農学研究科応用生命科学専攻<br>(主査)教授 植田 和光, 教授 阪井 康能, 教授 矢﨑 一史<br>学位規則第4条第1項該当
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Li, Chun-hei. "Characterization on the biochemical composition of collagen-hMSCs microspheres and their mechanical property during chondrogenic differentiation." Click to view the E-thesis via HKUTO, 2009. http://sunzi.lib.hku.hk/hkuto/record/B43278620.
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Bischof, Ashley Gibbs. "Extracellular Matrix as a Key Mediator of Mammary Tumor Cell Normalization." Thesis, Harvard University, 2013. http://dissertations.umi.com/gsas.harvard:10780.
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Some epithelial cancers can be induced to revert to quiescent differentiated tissues when combined with embryonic mesenchyme; however, the mechanism of this induction is unknown. This dissertation is based on the hypothesis that because extracellular matrix (ECM) plays a critical role during organ development in the embryo, it also may mediate the differentiation-inducing effects of embryonic mesenchyme on cancer cells. To test this hypothesis, I first optimized methods to isolate ECMs from whole tissues or cultured cells, and to repopulate them with cultured cells, using embryonic tooth as a model system. In Chapter 2, I describe these studies and use them to demonstrate that embryonic ECM is sufficient to regulate odontogenic signaling, cell fate decisions and histodifferentiation during normal tooth development. In Chapter 3, I adapt these methods to show that culture of breast cancer cells with ECM derived from embryonic mammary mesenchyme decreases tumor cell proliferation, and stimulates differentiation, including formation of hollow acini and ducts as well as enhanced expression of estrogen receptor-alpha and decreased migration. Further, when the inductive ECMs were injected into fast-growing breast tumors in mice, they significantly inhibited cancer expansion. Critically, the differentiation observed with ECM was the same as that observed in co-culture with mammary mesenchyme cells, showing that ECM is playing a dominant role in tumor cell normalization. In Chapter 4, I then set out to determine the mechanism by which embryonic ECM normalizes tumor cells, I analyzed the contributions of bound cytokines, ECM composition and mechanics. Western blot analysis revealed several bound growth factors, which remained following decellularization; however, removal of these growth factors using high salt washes had no effect on ECM-mediated normalization of tumors. Further, using proteomics analysis I identified eleven ECM proteins present only within inductive ECMs and by testing these proteins in 3D culture, I found three proteins -- collagen III, biglycan and SPARC -- that increased lumen formation to a similar extent as embryonic ECM. These data confirm that mesenchyme-induced tumor cell normalization is mediated by the insoluble ECM, and reveal the identity of some of the inductive molecules responsible for these effects.
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Angstmann, Michael [Verfasser], and Stefan [Akademischer Betreuer] Wölfl. "Characterization of cell-matrix interactions during multipotent mesenchymal stromal cell (MSC) differentiation / Michael Angstmann ; Betreuer: Stefan Wölfl." Heidelberg : Universitätsbibliothek Heidelberg, 2011. http://d-nb.info/1179230140/34.
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Ushenko, Yu A., A. P. Peresunko та Adel Bako Bouzan. "А new method of mueller-matrix diagnostics and differentiation of early oncological changes of the skin derma". Thesis, Hindawi Publishing Corporation, 2010. http://dspace.bsmu.edu.ua:8080/xmlui/handle/123456789/3144.
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The paper deals with investigation of the processes of laser radiation transformation by biological crystals networks using the singular optics techniques. The results obtained showed a distinct correlation between the points of “characteristic” values of coordinate distributions of Mueller matrix (Mik = 0, ± 1) elements and polarization singularities (L- and C-points) of laser transformation of biological crystals networks with the following possibility of Mueller-matrix selection of polarization singularity. The technique of Mueller-matrix diagnostics of pathological changes of skin derma is proposed.
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Egea, Alonso Virginia. "The role of matrix metalloproteinases and inflammatory cytokines on human mesenchymal stem cell invasiveness and differentiation capacity." kostenfrei, 2008. http://mediatum2.ub.tum.de/doc/649313/649313.pdf.
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Li, Chun-hei, and 李晉曦. "Characterization on the biochemical composition of collagen-hMSCs microspheres and their mechanical property during chondrogenicdifferentiation." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B43278620.
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Kim, Sung Min. "Glycosylation Properties Associated with Development and Differentiation of Spermatogonial Stem Cells in Mammalian Testis." Kyoto University, 2013. http://hdl.handle.net/2433/179363.
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Kyoto University (京都大学)<br>0048<br>新制・課程博士<br>博士(農学)<br>甲第17793号<br>農博第2014号<br>新制||農||1016(附属図書館)<br>学位論文||H25||N4784(農学部図書室)<br>30600<br>京都大学大学院農学研究科応用生物科学専攻<br>(主査)教授 今井 裕, 教授 久米 新一, 教授 松井 徹<br>学位規則第4条第1項該当
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Momtahan, Nima. "Extracellular Matrix from Whole Porcine Heart Decellularization for Cardiac Tissue Engineering." BYU ScholarsArchive, 2016. https://scholarsarchive.byu.edu/etd/6225.
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Heart failure is one of the leading causes of death in the United States. Every year in the United States, more than 800,000 people are diagnosed with heart failure and more than 375,000 people die from heart disease. Current therapies such as heart transplants and bioartificial hearts are helpful, but not optimal. Decellularization of porcine whole hearts followed by recellularization with patient-specific human cells may provide the ultimate solution for patients with heart failure. Great progress has been made in the development of efficient processes for decellularization, and the design of automated bioreactors. In this study, the decellularization of porcine hearts was accomplished in 24 h with only 6 h of sodium dodecyl sulfate (SDS) exposure and 98% DNA removal. Automatically controlling the pressure during decellularization reduced the detergent exposure time while still completely removing immunogenic cell debris. Stimulation of macrophages was greatly reduced when comparing native tissue samples to the processed ECM. Complete cell removal was confirmed by analysis of DNA content. General collagen and elastin preservation was demonstrated by SEM and histology. The compression elastic modulus of the ECM after decellularization was lower than native at low strains but there was no significant difference at high strains. Polyurethane casts of the vasculature of native and decellularized hearts demonstrated that the microvasculature network was preserved after decellularization. A static blood thrombosis assay using bovine blood was also developed. A perfusion bioreactor was designed and right ventricle of the decellularized hearts were recellularized with human endothelial cells and cardiac fibroblasts. An effective, reliable, and relatively inexpensive assay based on human blood hemolysis was developed for determining the remaining cytotoxicity of the cECM and the results were consistent with a standard live/dead assay using MS1 endothelial cells incubated with the cECM. Samples from the left ventricle of the hearts were prepared with 300 µm thickness, mounted on 10 mm round glass coverslips. Human induced pluripotent stem cells were differentiated into cardiomyocytes (CMs) and 4 days after differentiation, cardiac progenitors were seeded onto the decellularized cardiac slices. After 10 days, the tissues started to beat spontaneously. Immunofluorescence images showed confluent coverage of CMs on the decellularized slices and the effect of the scaffold was evident in the arrangement of the CMs in the direction of fibers. This study demonstrated the biocompatibility of decellularized porcine hearts with human CMs and the potential of these scaffolds for cardiac tissue engineering. Further studies can be directed toward 3D perfusion recellularization of the hearts and improving repopulation of the scaffolds with various cell types as well as adding mechanical and electrical stimulations to obtain more mature CMs.
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Cecil, Denise L. "The receptor for advanced glycation endproducts and S100A11 modulate pathologic chondrocyte differentiation and dysregulated cartilage matrix catabolism in osteoarthritis." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2008. http://wwwlib.umi.com/cr/ucsd/fullcit?p3315413.
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Thesis (Ph. D.)--University of California, San Diego, 2008.<br>Title from first page of PDF file (viewed September 3, 2008). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references (p. 104-126).
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Ariza, Carlos Atico. "Topography, extracellular matrix proteins, secreted molecules and endogenous electric fields cues that influence the differentiation of neural progenitor cells /." [Ames, Iowa : Iowa State University], 2009. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3389082.
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Shah, Mickey. "Cardiac Repair Using A Decellularized Xenogeneic Extracellular Matrix." University of Akron / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=akron1542631193281779.
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Griffith, Daniel Todd. "New methods for estimation, modeling and validation of dynamical systems using automatic differentiation." Texas A&M University, 2004. http://hdl.handle.net/1969.1/1408.
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The main objective of this work is to demonstrate some new computational methods
for estimation, optimization and modeling of dynamical systems that use automatic
differentiation. Particular focus will be upon dynamical systems arising in Aerospace
Engineering. Automatic differentiation is a recursive computational algorithm, which
enables computation of analytically rigorous partial derivatives of any user-specified
function. All associated computations occur, in the background without user
intervention, as the name implies. The computational methods of this dissertation are
enabled by a new automatic differentiation tool, OCEA (Object oriented Coordinate
Embedding Method). OCEA has been recently developed and makes possible efficient
computation and evaluation of partial derivatives with minimal user coding. The key
results in this dissertation details the use of OCEA through a number of computational
studies in estimation and dynamical modeling.
Several prototype problems are studied in order to evaluate judicious ways to use
OCEA. Additionally, new solution methods are introduced in order to ascertain the
extended capability of this new computational tool. Computational tradeoffs are studied
in detail by looking at a number of different applications in the areas of estimation,
dynamical system modeling, and validation of solution accuracy for complex dynamical
systems. The results of these computational studies provide new insights and indicate
the future potential of OCEA in its further development.
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Olsson, Katarina. "Population differentiation in Lythrum salicaria along a latitudinal gradient." Doctoral thesis, Umeå : Univ, 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-364.
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Reidinger, Amanda Zoe. "Changes in Passive and Dynamic Mechanical Environments Promote Differentiation to a Contractile Phenotype in Vascular Smooth Muscle Cells." Digital WPI, 2015. https://digitalcommons.wpi.edu/etd-dissertations/230.
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Every year, 400,000 coronary artery bypasses (CABG) are performed in the United States. However, one third of all patients who need a CABG cannot undergo the procedure because of the lack of suitable autologous blood vessels. Both synthetic and tissue engineered vascular grafts have been used clinically for vascular grafts or other surgical applications, but no small- diameter engineered vessels have yet been successfully used for CABG. The success of vascular tissue engineering is strongly dependent on being able to control tissue contractility and extracellular matrix (ECM) production to achieve balance between tissue strength and physiological function. Smooth muscle cells (SMCs), the main contributor of contractility in blood vessels, retain phenotypic plasticity, meaning they possess the ability to switch between a contractile and synthetic phenotype. In 2D culture, a number of biochemical and mechanical cues have been shown to promote the switch to a contractile phenotype in SMCs. However, achieving a stable contractile phenotype in 3D tissue has proven difficult. The work in this dissertation describes an investigation of how passive and dynamic environmental cues influence the smooth muscle phenotype. We studied the effects of substrate modulus in conjunction with changes in cell culture media composition on SMC phenotype in 2D and 3D cultures. Culturing SMCs in a low-serum culture medium resulted in an increase in SMC contractility in 2D cell culture but not in 3D cell-derived tissue. We found that, in SMCs cultured on soft substrates, the ability to modulate SMC phenotype in response to changes in media was diminished. Passively crosslinking the ECM of our cell-derived tissues with genipin resulted in modest increases in elastic modulus, though not enough to observe changes in SMC phenotype. Additionally, we investigated how dynamic cyclic mechanical stretch, in conjunction with cell culture medium, modified SMC contractility in cell and tissue cultures. SMCs increased contractile protein expression when exposed to dynamic stretch in 2D culture, even on soft substrates, which have previously been shown to inhibit phenotypic modulation. In 3D tissue rings, after mechanical stimulation, SMCs became more aligned, the tissue became tougher, and SMCs exhibited a measurable increase in contractile protein expression. In summary, we found that increasing substrate modulus, culturing in low serum cell culture medium, and imparting cyclic mechanical stretch can promote SMC differentiation and cellular alignment, and improve tissue mechanical properties. This information can be used to more accurately recapitulate vascular tissue for use in modeling or in the creation of tissue engineered blood vessels.
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Kurth, Ina [Verfasser], Carsten [Akademischer Betreuer] Werner, Tilo [Akademischer Betreuer] Pompe, and Martin [Akademischer Betreuer] Bornhäuser. "Hematopoietic Stem Cell Differentiation inside Extracellular Matrix functionalized Microcavities / Ina Kurth. Gutachter: Carsten Werner ; Martin Bornhäuser. Betreuer: Carsten Werner ; Tilo Pompe." Dresden : Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2011. http://d-nb.info/1067188878/34.
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Moncada, Diaz Silvia Juliana. "Repopulation and Stimulation of Porcine Cardiac Extracellular Matrix to Create Engineered Heart Patches." BYU ScholarsArchive, 2018. https://scholarsarchive.byu.edu/etd/8806.
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Heart failure is the main cause of death for both men and women in the United States. The only proven treatment for patients with heart failure is heart transplantation. The goal of this research is to create patches of tissue that could mimic the function of the native heart to repair the damaged portions of the heart. In this study, whole porcine hearts were decellularized to create a 3D construct that was recellularized with cardiomyocytes (CM) differentiated from human induced pluripotent stem (IPS) cells. At day 4 of differentiation, IPS-derived CMs were implanted onto cardiac extracellular matrix (cECM) and ten days after recellularization, the cells started to beat spontaneously. After implantation, the progenitor CMs continued to proliferate and populate the cECM. A live/dead assay showed the potential of the cECM as a scaffold suitable for recellularization. Confocal microscopy images were taken to evaluate the organization of the cells within the matrix and the impact of the cECM on the growth and maturation of the CMs. Representative cardiac Troponin T (cTNT) and vimentin immunostaining images of CMs derived from iPSCs, on cECM and on standard cell culture plates showed that the cECM allowed the cells to organize and form fibrils with the fibroblasts, compared with CMs cultured in regular culture plates. The timeline of implantation of the cells was a key factor for the development of the heart tissue constructs. Progenitor CMs seeded onto cECM showed better organization and the ability to penetrate 96 µm deep within the collagen fibers and align to them. However, mature CMs seeded onto the matrix showed a disorganized network with very reduced interaction of CMs with fibroblasts, forming two different layers of cells; CMs on top of fibroblasts. In addition, the depth of penetration of the mature CMs within the matrix was only 20 µm. To evaluate the impact of the addition of support cells to the CM monolayer cultures, CMs were co-cultured with human umbilical vein endothelial cells (HUVEC) and it was demonstrated that at ratios of 2:1 HUVEC:CM the beating rate of the CMs was improved from 20 to 112 bpm, additionally, the CM monolayer cultures showed a more synchronized beating pace after the addition of HUVECs. Pharmacological stimulation was performed on CM monolayer cultures using norepinephrine as a stimulator and the results showed that the beating pace of the CMs was improved to 116 bpm after 5 minutes of drug exposure. For future studies, inosculation of the tissue constructs could be performed with the incorporation of membrane proteins to understand the mechanotransduction of the cells. As a preliminary study, the action of dual claudins was evaluated with HUVEC cultures and the results showed the potential of these membrane proteins in the healing of the damaged cell membrane.
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Herrmann, Julien. "Memory-aware Algorithms and Scheduling Techniques for Matrix Computattions." Thesis, Lyon, École normale supérieure, 2015. http://www.theses.fr/2015ENSL1043/document.
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Dans cette thèse, nous nous sommes penchés d’un point de vue à la foisthéorique et pratique sur la conception d’algorithmes et detechniques d’ordonnancement adaptées aux architectures complexes dessuperordinateurs modernes. Nous nous sommes en particulier intéressésà l’utilisation mémoire et la gestion des communications desalgorithmes pour le calcul haute performance (HPC). Nous avonsexploité l’hétérogénéité des superordinateurs modernes pour améliorerles performances du calcul matriciel. Nous avons étudié lapossibilité d’alterner intelligemment des étapes de factorisation LU(plus rapide) et des étapes de factorisation QR (plus stablenumériquement mais plus deux fois plus coûteuses) pour résoudre unsystème linéaire dense. Nous avons amélioré les performances desystèmes d’exécution dynamique à l’aide de pré-calculs statiquesprenants en compte l’ensemble du graphe de tâches de la factorisationCholesky ainsi que l’hétérogénéité de l’architecture. Nous noussommes intéressés à la complexité du problème d’ordonnancement degraphes de tâches utilisant de gros fichiers d’entrée et de sortiesur une architecture hétérogène avec deux types de ressources,utilisant chacune une mémoire spécifique. Nous avons conçu denombreuses heuristiques en temps polynomial pour la résolution deproblèmes généraux que l’on avait prouvés NP-complet aupréalable. Enfin, nous avons conçu des algorithmes optimaux pourordonnancer un graphe de différentiation automatique sur uneplateforme avec deux types de mémoire : une mémoire gratuite maislimitée et une mémoire coûteuse mais illimitée<br>Throughout this thesis, we have designed memory-aware algorithms and scheduling techniques suitedfor modern memory architectures. We have shown special interest in improving the performance ofmatrix computations on multiple levels. At a high level, we have introduced new numerical algorithmsfor solving linear systems on large distributed platforms. Most of the time, these linear solvers rely onruntime systems to handle resources allocation and data management. We also focused on improving thedynamic schedulers embedded in these runtime systems by adding static information to their decisionprocess. We proposed new memory-aware dynamic heuristics to schedule workflows, that could beimplemented in such runtime systems.Altogether, we have dealt with multiple state-of-the-art factorization algorithms used to solve linearsystems, like the LU, QR and Cholesky factorizations. We targeted different platforms ranging frommulticore processors to distributed memory clusters, and worked with several reference runtime systemstailored for these architectures, such as P A RSEC and StarPU. On a theoretical side, we took specialcare of modelling convoluted hierarchical memory architectures. We have classified the problems thatare arising when dealing with these storage platforms. We have designed many efficient polynomial-timeheuristics on general problems that had been shown NP-complete beforehand
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Lim, Jeremy James. "The development of glycosaminoglycan-based materials to promote chondrogenic differentiation of mesenchymal stem cells." Diss., Georgia Institute of Technology, 2012. http://hdl.handle.net/1853/44849.
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Tissue engineering strategies represent exciting potential therapies to repair cartilage injuries; however, difficulty regenerating the complex extracellular matrix (ECM) organization of native cartilage remains a significant challenge. Cartilaginous ECM molecules, specifically chondroitin sulfate (CS) glycosaminoglycan, may possess the ability to promote and direct MSC differentiation down a chondrogenic lineage. CS may interact with the stem cell microenvironment through its highly negative charge, generation of osmotic pressure, and sequestration of growth factors; however, the role of CS in directing differentiation down a chondrogenic lineage remains unclear. The overall goal of this dissertation was to develop versatile biomaterial platforms to control CS presentation to mesenchymal stem cells (MSCs) in order to improve understanding of the interactions with CS that promote chondrogenic differentiation.
To investigate chondrogenic response to a diverse set of CS materials, progenitor cells were cultured in the presence of CS proteoglycans and CS chains in a variety of 2D and 3D material systems. Surfaces were coated with aggrecan proteoglycan to alter cell morphology, CS-based nano- and microspheres were developed as small particle carriers for growth factor delivery, and desulfated chondroitin hydrogels were synthesized to examine electrostatic interactions with growth factors and the role of sulfation in the chondrogenic differentiation of MSCs. Together these studies provided valuable insight into the unique ability of CS-based materials to control cellular microenvironments via morphological and material cues to promote chondrogenic differentiation in the development of tissue engineering strategies for cartilage regeneration and repair.
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Zanusso, Ilenia. "Acellular matrices as tool for renal progenitor differentiation studies and tissue engineering of blood vessels." Doctoral thesis, Università degli studi di Padova, 2013. http://hdl.handle.net/11577/3423024.
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AMs seem to be a very promising scaffold in TE and can be considered as temporary inductive site-appropriate templates to support the growth, differentiation, and function of the parenchymal cell population of each organ. Nowadays, TE techniques are used both to develop tissue substitutes ex vivo and as reliable tool to investigate cell behaviour, differentiation and proliferation in 3-dimentional environments.
In this work the following two different projects have investigated both potentialities using tissue-specific AMs:
1- influence of AMs on differentiation of kidney progenitor cells from amniotic fluid into mature renal cells;
2- AMs as biomaterial to develop vessel substitutes.
1- Kidney AMs (KAMs) were used to evaluate the differentiation of kidney progenitor cells from amniotic fluid into mature renal cells in order to better understand whether they could be suitable for future application in therapy. Renal progenitors were seeded into KAMs, which led them to proliferate, maintain podocyte phenotype and differentiate into tubular cells in vitro. To further evaluate the differentiative potential of KAMs, grafts composed of KAM with or without cells were intrarenal implanted into nude mice. In vivo, progenitors from amniotic fluid expressed mature renal markers, attracted inside KAMs murine cells presenting the same proteins and integrated into host structures.
2- Although autologous vascular grafts and artificial materials have been used for reconstruction of small diameter (5 mm) blood vessels, the poor availability of vessels and the occurrence of intimal hyperplasia and progressive atherosclerotic degeneration represent shortcoming of these vascular prostheses. Therefore, this study aimed to develop AM-based vascular grafts. Both AAMs alone and AAMs previously reendothelized with skin microvascular endothelial cells (ECs) were in vivo implanted and analyzed. The lack of reendothelization, leading to intimal hyperplasia and increased incidence of thrombosis observed in AAMs grafts, have indicated the need to provide in vitro an endothelial coverage of decellularized tissue. Indeed, grafts composed of AAM and skin microvasculature ECs shown good patency and no thrombi. Although these grafts appeared narrowed and a moderate hyperplasia has been detected in the inner layer, they presented two main advantages: they were obtained into a clinically relevant time frame and eliminated the need to remove healthy vessels for collecting autologous ECs.<br>Le matrici acellulari rappresentano uno scaffold promettente per l’ingegneria tessutale. Infatti, la matrice extracellulare costituisce un supporto sito-specifico che favorisce la crescita e il differenziamento delle cellule di qualsiasi organo.
Ad oggi, le tecniche dell’ingegneria tessutale sono utilizzate sia per lo sviluppo ex vivo di sostituti tessutali, che per studiare la proliferazione e la differenziazione delle cellule quando si trovano all’interno di uno scaffold tridimensionale.
In questo lavoro di tesi, i due seguenti progetti sono andati a valutare entrambe le potenzialità di matrici acellulari tessuto-specifiche:
1- valutazione della capacità della matrice acellulare di indurre il differenziamento di progenitori renali da fluido amniotico in cellule renali mature;
2- valutazione della matrice acellulare per la sostituzione di vasi sanguigni.
1- La matrice acellulare renale è stata utilizzata per valutare la capacità differenziativa di progenitori renali da fluido amniotico in modo da valutarne una futura applicazione terapeutica. I progenitori renali sono stati seminati sulla matrice acellulare renale, che, in vitro, ne ha promosso la proliferazione, il mantenimento del fenotipo podocitario e la differenziazione in cellule tubulari. Per valutare in vivo il potenziale differenziativo di queste cellule, la matrice da sola o ripopolata con le cellule è stata impiantata all’interno di un rene di topo nudo. I progenitori renali si sono ulteriormente differenziati, si sono integrati all’interno delle strutture tubulari dell’ospite e hanno promosso la migrazione di cellule differenziate murine all’interno dello scaffold.
2- La matrice acellulare di aorta è stata utilizzata per lo sviluppo di sostituti vasali. Nonostante vasi autologhi o costituiti di polimeri sintetici vengano già utilizzati nella pratica clinica per la ricostruzione di vasi di piccolo diametro (5 mm), numerosi sono gli svantaggi legati al loro utilizzo, quali l’iperplasia della tonaca intima e la degenerazione arteriosclerotica. Lo scopo di questo studio è stato quello di sviluppare sostituti vasali utilizzando come scaffold vasi decellularizzati. Matrici acellulari da sole o ripopolate con cellule endoteliali da microcircolo sono state impiantate nell’aorta di ratto Lewis. Come osservato negli impianti di sola matrice acellulare, la mancanza della copertura endoteliale portava all’iperplasia dell’intima e all’aumento di incidenza dei processi trombotici, sottolineando la necessità di reendotelizzare in vitro il vaso decellularizzato prima dell’impianto in vivo. Infatti, i sostituti vasali costituiti da matrice acellulare e cellule endoteliali da microcircolo hanno dimostrato di avere una buona resistenza al flusso e non presentavano trombi al loro interno. Sebbene questi vasi fossero assottigliati e mostrassero una leggera iperplasia della tonaca intima, questo approccio presentava due principali vantaggi: permetteva di ottenere sostituti vasali in un tempo clinicamente utile ed eliminava la necessità di rimuovere vasi sani per ottenere cellule endoteliali autologhe.
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Raihana, Nishat. "Optimization of Operational Overhead based on the Evaluation of Current Snow Maintenance System : A Case Study of Borlänge, Sweden." Thesis, Högskolan Dalarna, Mikrodataanalys, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:du-30548.
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This study analyzes snow maintenance data of Borlänge municipality of Sweden based on the data of 2017 to 2018. The goal of this study is to reduce operational overhead of snow maintenance, for example, fuel and time consumption of the snow maintenance vehicles, work hour of dedicated personnel, etc. Borlänge Energy equipped the snow maintenance vehicles with GPS devices which stored the record of the snow maintenance activities. The initial part of this study obtained insights out of the GPS data by using spatiotemporal data analysis. Derivation of the different snow maintenance treatments (plowing, sanding and salting) as well as the efficiency of the sub-contractors (companies which are responsible for snow maintenance) and inspectors (personnel who are liable to call the subcontractors if they think it is time for snow maintenance) are performed in the beginning of this study. The efficiency of the subcontractors and inspectors are measured to compare their performance with each other. The latter part of this study discusses a simulated annealing-based heuristics technique to find out optimal location for dispatching snow maintenance vehicles. In the existing system of snow maintenance, drivers of the maintenance vehicles decide to start location of maintenance work based on their experience and intuition, which might vary from one driver to another driver. The vehicle dispatch locations are calculated based on the availability of the vehicles. For example, if a subcontractor has three vehicles to perform snow maintenance on a specific road map, the proposed solution would suggest three locations to dispatch those vehicles. The purpose of finding the optimal dispatch location is to reduce the total travel distance of the maintenance vehicles, which yield less fuel and time consumption. The study result shows the average travel distance for 1, 3, and 5 vehicles on 15 road networks. The proposed solution would yield 18% less travel than the existing system of snow maintenance.
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Gower, Robert Mansel. "Diferenciação automática de matrizes Hessianas." [s.n.], 2011. http://repositorio.unicamp.br/jspui/handle/REPOSIP/306026.
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Orientador: Margarida Pinheiro Mello<br>Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Matemática, Estatística e Computação Científica<br>Made available in DSpace on 2018-08-18T06:57:47Z (GMT). No. of bitstreams: 1
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Previous issue date: 2011<br>Resumo: Dentro do contexto de programação não linear, vários algoritmos resumem-se à aplicação do método de Netwon aos sistemas constituídos pelas condições de primeira ordem de Lagrange. Nesta classe de métodos é necessário calcular a matriz hessiana. Nosso foco é o cálculo exato, dentro da precisão da máquina, de matrizes hessianas usando diferenciação automática. Para esse fim, exploramos o cálculo da matriz hessiana sob dois pontos de vista. O primeiro é um modelo de grafo que foca nas simetrias que ocorrem no processo do cálculo da hessiana. Este ângulo propicia a intuição de como deve ser calculada a hessiana e leva ao desenvolvimento de um novo método de modo reverso para o cálculo de matrizes hessianas denominado edge pushing. O segundo ponto de vista é uma representação puramente algébrica que reduz o cálculo da hessiana à avaliação de uma expressão. Esta expressão pode ser usada para demonstrar algoritmos já existentes e projetar novos. Para ilustrar, deduzimos dois novos algoritmos, edge pushing e um novo algoritmo de modo direto, e uma série de outros métodos conhecidos [1], [20, p.157] e [9]. Apresentamos estudos teóricos e empíricos sobre o algoritmo edge pushing. Analisamos sua complexidade temporal e de uso de memória. Implementamos o algoritmo como um driver do pacote ADOL-C [19] e efetuamos testes computacionais, comparando sua performance com à de dois outros drivers em dezesseis problemas da coleção CUTE [5]. Os resultados indicam que o novo algoritmo é muito promissor. Pequenas modificações em edge pushing produzem um novo algoritmo, edge pushing sp, para o cálculo da esparsidade de matrizes hessianas, um passo necessário de uma classe de métodos que calculam a matriz hessiana usando colorações de grafos, [14, 19, 30]. Estudos de complexidade e testes numéricos são realizados comparando o novo método contra um outro recentemente desenvolvido [30] e os testes favorecem o novo algoritmo edge pushing sp. No capítulo final, motivado pela disponibilidade crescente de computadores com multiprocesadores, investigamos o processamento em paralelo do cálculo de matrizes hessianas. Examinamos o cálculo em paralelo de matrizes hessianas de funções parcialmente separáveis. Apresentamos uma abordagem desenvolvida para o cômputo em paralelo que pode ser usando em conjunto com qualquer método de cálculo de hessiana e outra estratégia específica para métodos de modo reverso. Testes são executados em um computador com memória compartilhada usando a interface de programação de aplicativo OpenMP<br>Abstract: In the context of nonlinear programming, many algorithms boil down to the application of Newton's method to the system constituted by the first order Lagrangian conditions. The calculation of Hessian matrices is necessary in this class of solvers. Our focus is on the exact calculation, within machine precision, of Hessian matrices through automatic differentiation. To this end, we detail the calculations of the Hessian matrix under two points of view. The first is an intuitive graph model that focuses on what symmetries occur throughout the Hessian calculation. This provides insight on how one should calculate the Hessian matrix, and we use this enlightened perspective to deduce a new reverse Hessian algorithm called edge pushing. The second viewpoint is a purely algebraic representation of the Hessian calculation via a closed formula. This formula can be used to demonstrate existing algorithms and design new ones. In order to illustrate, we deduce two new algorithms, edge pushing and a new forward algorithm, and a series of other known Hessian methods [1], [20, p.157] and [9]. We present theoretical and empirical studies of the edge pushing algorithm, establishing memory and temporal bounds, and comparing the performance of its computer implementation against that of two algorithms available as drivers of the software ADOL-C [14, 19, 30] on sixteen functions from the CUTE collection [5]. Test results indicate that the new algorithm is very promising. As a by-product of the edge pushing algorithm, we obtain an efficient algorithm, edge pushing sp, for automatically obtaining the sparsity pattern of Hessian matrices, a necessary step in a class of methods used for computing Hessian matrices via graph coloring, [14, 19, 30]. Complexity bounds are developed and numerical tests are carried out comparing the new sparsity detection algorithm against a recently developed method [30] and the results favor the new edge pushing sp algorithm. In the final chapter, motivated by the increasing commercial availability of multiprocessors, we investigate the implementation of parallel versions of the edge pushing algorithm. We address the concurrent calculation of Hessian matrices of partially separable functions. This includes a general approach to be used in conjunction with any Hessian software, and a strategy specific to reverse Hessian methods. Tests are carried out on a shared memory computer using the OpenMP paradigm<br>Mestrado<br>Analise Numerica<br>Mestre em Matemática Aplicada
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Hogrebe, Nathaniel James. "Modifying Cellular Behavior Through the Control of Insoluble Matrix Cues: The Influence of Microarchitecture, Stiffness, Dimensionality, and Adhesiveness on Cell Function." The Ohio State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=osu1470674560.
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Sandjeu, Yongoua. "Étude prospective pour la recherche et la caractérisation d’éléments desmosomaux et périkératinocytaires dont l’expression est liée à la différenciation épidermique." Thesis, Lyon 1, 2010. http://www.theses.fr/2010LYO10326.
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L’épiderme est un tissu épithélial stratifié et kératinisé, majoritairement composé de kératinocytes. La cohésion de l’épiderme, élémentaire à la fonction-barrière et donc à la protection de l’organisme, est assurée grâce à des systèmes de jonctions intercellulaires, notamment les desmosomes. Comme l’indiquent nos résultats d’étude de la desmosealine, un protéoglycanne épidermique présent dans la partie extracellulaire des desmosomes, la composition de ces jonctions n’est pas encore entièrement élucidée. Les éléments matriciels issus des espaces extracellulaires de l’épiderme peuvent être incorporés au sein des desmosomes et participer ainsi à la régulation de la différenciation et la cohésion épidermiques. Nous avons mis au point une méthode permettant d’isoler les desmosomes épidermiques humains utilisables pour créer de nouveaux anticorps et favorisant la caractérisation biochimique de ces structures. Un nouvel anticorps monoclonal reconnaissant un antigène situé à la surface des kératinocytes, dont l’expression varie en fonction du degré de différenciation kératinocytaire, a été crée. A l’aide de cet anticorps, nous avons entrepris la caractérisation biochimique et par spectrométrie de masse de l’antigène associé. Nous avons ainsi développé de nouveaux outils biologiques et techniques utilisables pour l’étude des desmosomes et de leurs éléments issus de la matrice extracellulaire épidermique<br>Epidermis is a stratified, keratinized epithelial tissue, mostly composed of keratinocytes. Epidermal barrier function provided by epidermis is essential for protection of the organism and largely depends on cell cohesion. Desmosomes constitute the most prominent cell-to-cell junction system involved in this function. As indicated by our results of studies on desmosealin, an epidermal proteoglycan present in the extracellular parts of desmosomes, the composition of these junctions is not yet completely resolved. Elements of the intercellular matrix can be incorporated into desmosomes and thus participate in the regulation of the epidermal differentiation and cohesion. We established a method to isolate human epidermal desmosomes in order to create new antibodies allowing the biochemical characterization of new desmosomal components. A new monoclonal antibody has been generated. It recognizes an antigen located at the keratinocyte surface with an expression pattern depending on the level of keratinocyte differentiation. Using this antibody, we have engaged the biochemical and mass spectrometry characterization of the corresponding antigen. This work contributes to the development of new biological and technical tools useful for studies of desmosomes and of their components issued from the epidermal extracellular matrix
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Doroski, Derek M. "The effects of tensile loading and extracellular environmental cues on fibroblastic differntiation and extracellular matrix production by mesenchymal stem cells." Diss., Georgia Institute of Technology, 2011. http://hdl.handle.net/1853/39523.
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Ligament/tendon tissue engineering has the potential to provide therapies that overcome the limitations of incomplete natural healing responses and inadequate graft materials. While ligament/tendon fibroblasts are an obvious choice of cell type for these applications, difficulties associated with finding a suitable cell source have limited their utility. Mesenchymal stem cells/marrow stromal cells (MSCs) are seen as a viable alternative since they can be harvested through routine medical procedures and can be differentiated toward a ligament/tendon fibroblast lineage. Further study is needed to create an optimal biomaterial/biomechanical environment for ligament/tendon fibroblastic differentiation of MSCs. The overall goal of this dissertation was to improve the understanding of the role that biomechanical stimulation and the biomaterial environment play, both independently and combined, on human MSC (hMSC) differentiation toward a ligament/tendon fibroblast phenotype. Specifically, the effects of cyclic tensile stimuli were studied in a biomaterial environment that provided controlled presentation of biological moieties. The influence of an enzymatically-degradable biomaterial environment on hMSC differentiation was investigated by creating biomaterials containing enzymatically-cleavable moieties. The role that preculture may play in tensile responses of hMSCs was also explored. Together, these studies provided insights into the contributions of the biomaterial and biomechanical environment to hMSC differentiation toward a ligament/tendon fibroblast phenotype.
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Juignet, Laura. "Effets de la macro-architecture du substrat sur l'activité et la différenciation des ostéoblastes." Thesis, Lyon, 2016. http://www.theses.fr/2016LYSES060/document.
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In vivo, les cellules osseuses évoluent dans un microenvironnement complexe, tridimensionnel et interagissent avec celui-ci à de nombreuses échelles, depuis le nanomètre (tropocollagène) jusqu’à des structures de plusieurs centaines de micromètres (trabécules). Paradoxalement, la majeure partie de nos connaissances sur la physiologie cellulaire est issue d’expériences réalisées sur des cellules cultivées sur du plastique et en deux dimensions. Ces différences ne peuvent qu’avoir une influence sur le comportement des cellules, qui n’entretiennent plus les mêmes relations spatiales entre elles, ainsi qu’avec leur environnement. De plus, si ces dernières années, nombre d’études ont été réalisées sur l’influence de la topographie à des échelles nano et micrométriques, peu d’études ont montré le rôle de la géométrie du substrat à une échelle tissulaire, soit au sein de structures supérieures à 100 µm. Afin d’étudier l’influence de la macroarchitecture du substrat sur le comportement cellulaire, des céramiques en hydroxyapatite à architecture contrôlée ont été ensemencées avec des cellules primaires de calvaria de souris. Une première étude a été entreprise sur des substrats macroarchitecturés, présentant des sillons de différentes géométries : sillons semi-circulaires (Wave), sillons triangulaires à angle de 90° ou à angle de 45°. Plus la géométrie du substrat était refermée (45°>90°>Wave), plus la différenciation ostéoblastique était rapide. Cela s’est traduit par une augmentation des niveaux d’expression génique et protéique d’ostéocalcine et de sclérostine, indiquant la présence d’ostéocytes au sein de l’important tissu déposé par les cellules. De plus, au sein de la géométrie à l’angle le plus fermé (i.e. « 45° »), des structures fibreuses minéralisées, orientées parallèlement au fond du substrat ont été observées. Cette orientation s’est confirmée au niveau cellulaire, avec une orientation similaire des fibres de stress et un étirement des noyaux cellulaires. La géométrie du substrat influence donc le comportement des cellules en modifiant très probablement leur signalisation intracellulaire. Ces investigations ont été poursuivi par le développement d’un modèle d’ostéogénèse 3D sous perfusion au sein du bioréacteur BOSE ElectroForce® 5270 BioDynamic®de la plateforme Equipex IVTV, afin d’explorer les interactions cellulaires-substrat en réponse à des contraintes mécaniques (forces de cisaillement). Le dépôt tissulaire était particulièrement abondant au sein des pores triangulaires à angle de 45°, confirmant les données obtenues sur les substrats macroarchitecturés et laissant penser que ce type de pores est le plus à même de permettre une différenciation ostéoblastique optimale. Les résultats de ces travaux pourront permettre des avancées dans la compréhension de la biologie de l’os, mais également dans la conception d’implants innovants destinés à la réparation de défaux osseux, avec une ostéointégration stimulée via la présence de structures à géométrie fermée, tel que des sillons triangulaires à angles de 45°<br>In vivo, cells reside in a complex and three-dimensional microenvironment, with which they interact at multiple scales, from the nanometer (tropocollagen) to structures of several hundred of micrometers (trabeculae). However, most of our knowledge on cell physiology has been obtained from cells grown in Petri dishes, on plastic and in two dimensions. In those conditions, the spatial relationships between cells and their environment can only be deeply modified. Moreover, if the impact of substrate closure at a cellular level is particularly well documented, very few studies have shown its role at a tissue level (i.e. greater than 100 µm), and thus focused mostly on the matrix deposition rather than on the osteoblastic differentiation. In order to study the effects of substrate macroarchitecture on cells, primary mouse calvarial cells were seeded on hydroxyapatite-based bioceramics, made from wax molds by 3D printing. A first study was conducted on macroarchitectured substrates. These bioceramics have three patterns of different degrees of closure: semi-circular grooves (Wave), triangular grooves with 90° angle and triangular grooves with 45° angle. The tighter was the substrate geometry (45°> 90°> Wave), the faster was osteoblastic differentiation. This resulted in increased levels of gene and protein expression of osteocalcin and sclerostin, indicating the presence of osteocytes inside the tissue layed by cells. Moreover, in the tightest geometry (i.e. 45°), mineralized fibrous structures, oriented parallel to the bottom substrate were observed. This orientation was confirmed at the cellular level, with a similar orientation of stress fibers and a stretch of cell nuclei. Thus, the substrate macroarchitecture influences the cellular behavior by, most likely, modifying the intracellular signaling. These investigations were pursued with the development of a 3D model of osteogenesis under perfusion, in the BOSE 5270 ElectroForce® BioDynamic® bioreactor of the IVTV Equipex platform, to explore cell-substrate interactions in response to mechanical stress (shear forces). Tissue deposition was particularly abundant in the triangular pores with 45° angles, confirming our previous observations and suggesting that this geometry was able to promote osteoblast differentiation.Our results could lead to breakthroughs in the understanding of the bone biology but also in the design of innovative implants for the repair of bone defects, with a stimulated osseointegration throught the presence of structures with closed geometries, such as triangular grooves with 45° angles
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Hempel, Ute, Carolin Preissler, Sarah Vogel, et al. "Artificial Extracellular Matrices with Oversulfated Glycosaminoglycan Derivatives Promote the Differentiation of Osteoblast-Precursor Cells and Premature Osteoblasts." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2015. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-165309.
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Sulfated glycosaminoglycans (GAG) are components of the bone marrow stem cell niche and to a minor extent of mature bone tissue with important functions in regulating stem cell lineage commitment and differentiation. We anticipated that artificial extracellular matrices (aECM) composed of collagen I and synthetically oversulfated GAG derivatives affect preferentially the differentiation of osteoblast-precursor cells and early osteoblasts. A set of gradually sulfated chondroitin sulfate and hyaluronan derivatives was used for the preparation of aECM. All these matrices were analysed with human bone marrow stromal cells to identify the most potent aECM and to determine the influence of the degree and position of sulfate groups and the kind of disaccharide units on the osteogenic differentiation. Oversulfated GAG derivatives with a sulfate group at the C-6 position of the N-acetylglycosamine revealed the most pronounced proosteogenic effect as determined by tissue nonspecific alkaline phosphatase activity and calcium deposition. A subset of the aECM was further analysed with different primary osteoblasts and cell lines reflecting different maturation stages to test whether the effect of sulfated GAG derivatives depends on the maturation status of the cells. It was shown that the proosteogenic effect of aECMwasmost prominent in early osteoblasts. [ABSTRACT FROM AUTHOR]