WorldCat Identities

Wilhelm, Claire (1975-....).

Overview
Works: 16 works in 22 publications in 2 languages and 24 library holdings
Roles: Thesis advisor, Opponent, 958, Other, Author
Publication Timeline
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Most widely held works by Claire Wilhelm
Elaboration et caractérisation d'agents de contraste IRM pour le ciblage des intégrines [alpha]v[beta]₃ by Julie Bolley( Book )

2 editions published in 2014 in French and held by 3 WorldCat member libraries worldwide

L'imagerie de l'angiogénèse tumorale représente actuellement un domaine majeur de la recherche pour la détection précoce des cancers et le développement de nouveaux traitements des tumeurs. Les cellules endothéliales des néovaisseaux formés surexpriment l'intégrine [alpha]v[beta]₃, qui se lie sélectivement aux peptides contenant la séquence Arg-Gly-Asp (RGD). Le processus angiogénique joue également un rôle dans le développement d'autres pathologies telles les maladies cardiovasculaires. Le but de ce projet est ainsi de concevoir un agent de contraste bimodal (IRM et fluorescence) ciblant les intégrines [alpha]v[beta]₃ pour une détection précoce de l'angiogénèse. Des nanoparticules superparamagnétiques d'oxyde de fer ont été fonctionnalisées en surface par des agents complexants de type cathécol ou bisphosphonate présentant des fonctions réactives terminales, acide carboxylique ou alcyne. L'efficacité du couplage de diverses molécules (fluorophores, PEG, RGD) par chimie des carbodiimides ou par chimie click (réactions de Huisgen ou thiol-yne) a été comparée. La stabilité des différentes sondes dans le sérum et leur potentiel en tant qu'agent de contraste IRM a été évalué. L'affinité vis-à-vis des intégrines a été étudiée par résonance plasmonique de surface et par dosage de liaisons sur support solide en présence d'un compétiteur radioactif. Dans le but d'optimiser les propriétés d'agents de contraste IRM, une étude de l'influence de la taille et de la forme des nanoparticules a été réalisée. Les premières évaluations in vitro et in vivo des nanoplateformes ont été entreprises. Parallèlement, une nanoplateforme théranostique, alliant diagnostic et thérapie, a été envisagée
Impact d'une perturbation mécanique ou photo-chimique sur le trafic intracellulaire by Kelly Aubertin( Book )

3 editions published between 2014 and 2017 in English and French and held by 3 WorldCat member libraries worldwide

The cell cytoplasm is crowded with membrane-delimited compartments, permanently communicating with each other. Such communication is permitted by active transport, also called intracellular trafficking, of vesicles along the cytoskeleton (actin filaments, microtubules), and mediated by molecular motors. In order to perturbate this intracellular trafficking, two different ways to apply controlled physical stresses have been performed. The first perturbation is a mechanical one: we used magnetic endosomes to probe and stress the cell body. To obtain them we internalized magnetic nanoparticles into mesenchymal stem cells (MSC) through the natural endocytosis pathway. These endosomes align into chains in the presence of a magnetic field. The mechanical perturbation then consists in applying a rotational magnetic field on these chains. When comparing the activity before and after a shear stress, we observed a decrease in the intracellular activity. The second perturbation has a photochemical origin, through the excitation of an internalized photosensitizer molecule (m-THPC or TPCS2a). By combining measurements of local cytoplasmic viscosity and intracellular activity, we found that photo-activation induced only a slight increase in viscosity while a massive slowing down of trafficking was observed. These effects are correlated with depolymerization of the microtubule network. The experiments demonstrate that these two photochemical agents have different intracellular impacts. Eventually, we studied a second effect of the photochemical perturbation which is the massive and rapid emission of extracellular vesicles
Développement d'une sonde intracellulaire : l'endosome magnétique by Claire Wilhelm( Book )

2 editions published in 2002 in French and held by 2 WorldCat member libraries worldwide

Manipulations magnétiques à l'échelle de la cellule by Damien Robert( Book )

2 editions published in 2010 in French and held by 2 WorldCat member libraries worldwide

The use of magnetic nanoparticles offers new potentialities to study the living. On the one hand, they can be manipulated by external magnetic fields, and on the other hand, due to their nanoscale size, they can be inserted inside cells, within small vesicles: the "endosomes". In this thesis, it was possible to handle these "magnetic endosomes" in the intracellular space to probe its mechanical properties and to assess the driving forces responsible for the movement of endosomes along microtubules. In parallel, the presence of magnetic nanoparticles into cells made it possible to have an influence on their movement with a remote magnetic force. This has been used to magnetically seed stem cells in a three-dimensional biodégradable matrix and to sort cells in a microfluidic device according to their magnetization
Nanostructures magnétiques pour le diagnostic et la thérapie : hyperthermie, relaxation magnétique et devenir dans l'organisme by Michaël Levy( Book )

2 editions published in 2011 in French and held by 2 WorldCat member libraries worldwide

This thesis sets itself into the field of research and optimization of medical applications using magnetic nano-objects. The first part describes an application called magnetic hyperthermia. It consists in using nanopar-ticles as local heating mediators, submitting them to a high frequency magnetic field. After recalling the hyperthermia mechanisms as well as the associated therapeutic constraints, we report a study on different kinds of nanoparticles and other more complex Systems. The second part is focused on MRI contrast agent properties of magnetic nanoparticles. We present the role of nanoparticles in this diagnostic technique and the relaxation mechanisms they induce. The longitudinal relaxation time T1 is theoretically evaluated and compared with experiments. At last, we investigate the cellular internalization effect on the time T1. The last part focuses on the evolution of magnetic nanoparticles injected in the organism. We first investigate their long term in vivo biotransformation (using different magnetic methods to follow their evolution) and then, we consider the impact of cellular metabolism on their magnetic properties
Local control of magnetic objects in microfluidic channels by Caroline Derec( )

1 edition published in 2009 in English and held by 2 WorldCat member libraries worldwide

Agrégats multicellulaires magnétiques : mécanique des tissus et biodégradation des nanomatériaux by François Mazuel( )

1 edition published in 2016 in French and held by 1 WorldCat member library worldwide

Les nanoparticules d'oxyde de fer ont récemment été envisagées comme outils pour l'ingénierie tissulaire. Elles sont internalisées par les cellules qui deviennent alors magnétiques. Des forces magnétiques peuvent ainsi être appliquées à distance sur ces cellules pour contrôler leur organisation spatiale et temporelle, et former un tissu. Ces applications posent la question du devenir des nanoparticules, qui conditionne in fine leur utilisation clinique. Ce travail s'inscrit dans ce cadre et comporte deux axes.La première partie traite de l'étude des propriétés mécaniques et rhéologiques de tissus biologiques modèles, les agrégats multicellulaires. Une combinaison de méthodes magnétiques est proposée pour fabriquer et stimuler des tissus magnétiques de taille et de forme contrôlées. Ces agrégats magnétiques sont soumis à distance à des contraintes magnétiques d'écrasement. L'étude de leur déformation permet d'explorer des caractéristiques statiques et dynamiques rarement étudiées à l'échelle tissulaire (tension de surface, loi puissance, non linéarité). La deuxième partie se concentre sur l'évolution à moyen terme des nanoparticules dans leur environnement tissulaire, au cœur des agrégats. En combinant ce tissu modèle avec des méthodes de quantification magnétique, nous avons pu mettre en évidence une dégradation massive d'origine endosomale, sans pour autant impacter de manière importante l'homéostasie du fer. De plus, le modèle tissulaire mis en place permet d'étudier la biodégradation intracellulaire de n'importe quel type de nanoparticules. Nous l'avons testé avec des nano-architectures plus complexes: nanocubes, nanodimers, ou nanoparticules magnéto-plasmoniques
Synthesis of magnetic and thermosensitive iron oxide based nanoparticles for biomedical applications by Gauvin Hemery( )

1 edition published in 2017 in English and held by 1 WorldCat member library worldwide

This thesis reports the development of hybrid nanoparticles made of an inorganic iron oxide core and an organic shell for medical applications. Iron oxide nanoparticles (IONPs) were produced by the polyol pathway, leading to a good control over their crystallinity and morphology (monocore or multicore). IONPs with diameters in the range of 4 to 37 nm were produced. Their properties as MRI contrast agents were assessed and compared, for possible theranostic applications. They can be used for treating cancer by magnetic hyperthermia, and as contrast agents for MR imaging. The surface of the IONPs was modified to bring stability in biological conditions, as well as new functionalities. Poly(ethylene glycol) was grafted for its stealth property, poly(2-dimethylaminoethyl methacrylate) (PDMAEMA) and elastin-like polypeptides (ELPs) for their thermosensitive capabilities, and a DY700 fluorescent probe was grafted for tracking nanoparticles in vitro and in vivo. The magnetic and thermosensitive properties of the nanoparticles were studied using a unique set-up combining magnetic hyperthermia with dynamic-light scattering. This set-up allowed measuring the elevations of temperature of the samples as well as variations in diameter and backscattered intensity. Monocore and multicore IONPs grafted with PEG, and monore IONPs grafted with a diblock ELP were tested in vitro. Their interactions with glioblastoma cells were studied, from the internalization pathway inside the cells to their cytotoxic effect (up to 90 %) under magnetic hyperthermia. In vivo, nanoparticles intravenously injected in mice accumulated in the tumors. Intratumoral administration followed by magnetic hyperthermia treatment led to elevations of temperature of up to 10 °C, with a significant effect on the tumor activity
<> by Julie Bolley( )

1 edition published in 2014 in French and held by 1 WorldCat member library worldwide

Thérapie cellulaire : comment contrôler l'organisation cellulaire ? by Guillaume Frasca( Book )

1 edition published in 2010 in French and held by 1 WorldCat member library worldwide

Using a universal technique of magnetic labelling of living cells, we achieve the formation of three-dimensional multicellular assemblies by applying a localised magnetic force. This active control of cell adhesion allows us to determine the final aggregate dimensions, and yields a broad range of applications, from inter-cellular interactions study to tissue engineering. The cohesion of an assembly containing hundreds of thousands of cells can be linked to its relaxation dynamics observed after the force withdrawal ; this kinetics relies on inter-cellular interactions within the assembly. Besides a qualitative distinction between cell types according to the specificity of adhesive mechanisms at play, we observe sensible variations due to the expression of E-cadherin, a tranmembrane protein involved in intercellular adhesion. Through analogies with granular media and foam physics, we build simple models to correlate macroscopic behavior and individual cell properties. Active magnetic patterning can be applied to mesenchymal stem cells chondrogenic differentiation (formation of cartilage). Cellular pre-condensation is crucial: usually obtained though centrifugation, it is here obtained via the application of a magnetic force throughout differentiation. Magnetic labelling innocuity has been tested as a prerequisite. This magnetic condensation allows us to form full differentiated aggregates of higher dimensions
Nanoparticules d'or à couronne polymère modulable : synthèse, interactions avec les systèmes biologiques et propriétés de radiosensibilisation by Marine Le Goas( )

1 edition published in 2019 in French and held by 1 WorldCat member library worldwide

These past twenty years, there has been a great increase in the number of studies concerning the use of nanoparticles for medical applications, especially for cancer treatment. In particular, radiosensitizing effects of metal nanoparticles have been studied a lot in radiotherapy, in order to reduce the side effects created by the irradiation of healthy tissues surrounding the tumor. In this work, we focused on polymer-grafted gold nanoparticles. The polymer corona both ensured a great stability of the objects and allowed to change their physico-chemical properties, in order to study their impact on the nanoparticles behavior. We used polymethacrylates which were obtained through controlled radical polymerization and acted as ligands during the gold nanoparticles synthesis. A library of nano-objects with different properties was established by varying both molar mass and chemical nature of (co)polymers. Thorough characterization, including by small-angle radiation scattering, revealed similar structures for all synthesized objects. Grafting of one chemotherapy agent, doxorubicin, and two proteins was also performed on polymer ligands. Interactions between these various nanoparticles and biological systems were studied in detail. Special attention was given to the impact of polymer corona properties. Four aspects were examined: colloidal stability in biological media, ability to diffuse inside the extracellular matrix, cellular uptake, and cytotoxicity. All studied ligands ensured a great stability. Regarding the other aspects, systematic comparison of the results obtained for the whole library highlighted a strong impact of the ligands nature, especially the presence of positive charges or hydrophobic segments. We have also shown that grafted doxorubicin and protein kept their toxic and targeting properties respectively. Lastly, the prospect of using these nanoparticles for radiosensitization led us to study their behavior under radiations. When irradiated, their structure was found stable. Combining them with radioiodine (internal radiotherapy) showed a great radiosensitizing effect, both in vitro and in vivo, but experiments with protontherapy (external radiotherapy) revealed different behaviors depending on the type of radiations. We also investigated the use of particle-induced X-ray emission to detect nanoparticles in situ, during protontherapy treatment
Magnetic approaches to form and to stimulate three-dimensional tissue models by Gaëtan Mary( )

1 edition published in 2020 in English and held by 1 WorldCat member library worldwide

This thesis presents the use of magnetic forces as a tool to form and to mechanically stimulate multicellular aggregates. These 3D structures, composed of interconnected cells, are considered as relevant models of biological tissues. Herein, magnetic cells are spatially controlled to create magnetic multicellular aggregates presenting specific shapes and sizes, and to subject them to remote mechanical stimuli without any external scaffold. Three different subjects are addressed: (i) the use of magnetic approaches to perform tissue rheology (ii) the use of magnetic forces to apply large anisotropic deformation on tumor models (iii) finally, the use of magnetic forces to enhance the differentiation of multicellular aggregates composed of cardiac muscle and skeletal muscle precursors
Approches interdisciplinaires du domaine des vésicules extracellulaires : nouvelles méthodes et outils pour le transfert en clinique en médecine régénérative et délivrance de médicaments by Max Piffoux( )

1 edition published in 2018 in English and held by 1 WorldCat member library worldwide

Extracellular Vesicles, encompassing exosomes, microvesicles, apoptotic bodies are nanosized vesicles secreted by most cells of the organism, that demonstrated physiologic and physio-pathologic roles in various processes like hemostasis, metastasis, information transfer through biological macromolecules or more recently in inflammation resolution in regenerative medicine. Therapeutic use of these EVs, in particular as drug delivery systems or as a regeneration triggering agent is of a major interest, for example the use Mesenchymal Stem Cells derived EVs after myocardial infarction or stroke. EV recapitulate their parental cell effect and benefit from unique opportunities like off the shelf availability, low immunogenicity and no anarchic differentiation or pulmonary embolism. However, major obstacles are still to be faced in the field, like the EV drug loading, engineering, targeting, characterization, delivery method and GMP high yield production toward clinical translation. We developed new methods to respond to these needs at the crossroad of biology, physics, pharmacy and medicine, and discovered meanwhile that some of these techniques can be used in other fields and indications. As an example, a new liquid cell transmission electron microscopy labeling method was used to investigate live in situ at the nanoscale level EVs behavior, and can be used for other “soft” materials like liposomes or biology processes. The PEG induced liposome/EV fusion method was designed to produce biological/synthetic hybrids with engineered membrane properties and drug loading. A first response to the production problem was made designing a microfluidic chip allowing shear stress application to trigger EV production. The concept of shear stress triggered EV release was also used in the design of 2nd generation system for high yield, scalable and compliant with Good Manufacturing Practice, EV production method that uses a controlled shear stress to induce EV secretion. These EVs were tested in regenerative medicine models of fistula healing and chronic heart insufficiency confirming the interest of a new local delivery method using thermosensitive gels and their potency compared to parental cells. Our team is now exploring the scale-up, immunogenicity, and stability of these EVs and benchmarking their cost/efficiency in various models to pave the way toward the democratization of EV-based regenerative medicine through a company/platform creation
Suivi in vivo de cellules immunitaires par imagerie multimodale by Solenne Vaillant( )

1 edition published in 2019 in French and held by 1 WorldCat member library worldwide

Recent clinical trial results have demonstrated the efficacy of immunotherapy in cancer patients. This type of therapy involves treating cancer cells by stimulating the patient's immune defenses. The aim of this thesis project is to develop a biomarker of efficacy for this therapy, in order to better understand the biological mechanisms involved, and to have an early and non-invasive indicator of the patient's response to immunotherapy. To do this, two imaging techniques (MRI and PET) were used as in vivo monitoring tools for the biodistribution of different populations of immune cells. The first step of this work was to establish different protocols for labeling immune cells. For the PET approach, the immune cells were labeled with Zirconium 89; and for MRI, two labeling techniques were studied: the first uses iron nanoparticles, and the other uses micelles loaded with Fluorine 19. After validation of their non-toxicity, the sensitivity of each labeling was evaluated in vitro, then in vivo in a second step, thus making it possible to study the biodistribution of the immune cells after different types of injections. The labeling with Zirconium 89 was then tested on different animal models of immunotherapies (PD1/PDL1 for example). Finally, since direct markings do not allow optimal cellular monitoring in the long term, a cell labeling approach using reporter genes has been considered. It involved modifying the genome of the immune cells so that they could express an enzyme (for example the viral thymidine kinase HSV1-TK) or a transporter (such as the NIS iodine transporter) allowing the internalization of a radioactive tracer in vivo, and thus be able to carry out indirect labeling of the cells
Nanoparticules en environnement cellulaire : Impact de la nano-architecture sur l'internalisation, la biodégradation et les fonctionnalités thérapeutiques. by Anouchka Plan( )

1 edition published in 2019 in French and held by 1 WorldCat member library worldwide

Les nanoparticules inorganiques représentent des solutions innovantes dans le domaine médical aussi bien dans le diagnostic que la thérapie.La première partie de cette thèse aborde les interactions entre les nanoparticules magnétiques et les cellules souches. Nous avons cherché à mieux comprendre les paramètres influençant l'internalisation et la biodégradation et mis en évidence un impact de la fonctionnalisation, des protéines présentes dans le milieu de culture et de l'agrégation. L'impact des nanoparticules sur la différenciation des cellules souches a permis de mettre en évidence un processus de remagnétisation de nanoparticules dégradées pour certaines voies de différenciation.Dans la seconde partie, nous nous sommes intéressés à des thérapies anti-cancéreuses par hyperthermie et plus précisément l'impact du confinement intracellulaire. Ainsi nous avons montré que le confinement intracellulaire peut inhiber complètement le chauffage généré par hyperthermie magnétique mais qu'il peut au contraire faciliter la photothermie à des longueurs d'onde biologiquement compatibles. Enfin, la combinaison de la photothermie et d'une molécule anti-cancéreuse a permis d'obtenir une thérapie plus efficace avec moins d'effets secondaires
Magnétisme et cellules souches : nouveaux outils pour l'ingénierie tissulaire et l'étude de la différenciation cellulaire by Vicard Du( Book )

1 edition published in 2015 in French and held by 1 WorldCat member library worldwide

Le concept d'ingénierie tissulaire, a pour but de développer de nouvelles technologies d'assemblages cellulaires, moléculaires et matricielles et des stratégies thérapeutiques aussi bien pour le remplacement de tissus, que pour la création de modèles pour l'évaluation de médicaments ou pour des études plus fondamentales telle la différentiation cellulaire. Dans le cadre de notre thèse, nous avons développé de nouvelles stratégies magnétiques en exploitant la manipulation 3D de cellules souches rendues magnétique vers le concept d'assemblage cellulaire en agrégat organisé en 3D. D'un côté, nous avons démontré qu'il est possible de créer des structures purement cellulaires à partir de cellules souches mésenchymateuse (MSCs) sous forme de bâtonnets, de taille millimétrique. Sachant que ces cellules possèdent la capacité de se différencier en cellules de l'os, cartilage et adipeuses. De l'autre nous avons réussi à confiner des MSCs dans des matrices de soutien poreux pour optimiser la différenciation vers le cartilage et son utilisation en tant que biomatériaux. L'autre objectif de la thèse répond davantage aux problématiques actuelles du contrôle de la différentiation de cellules souches embryonnaires pluripotente. Derrière le potentiel de ces cellules, se cache un problème majeur. En effet, sans aucun contrôle, ces cellules donnent lieu à un amas hétérogène de types cellulaires, qui complique la finalité thérapeutique. L'idée de cette seconde partie de la thèse est d'exporter les techniques magnétiques développées auparavant dans le but d'explorer le rôle de forces mécaniques cycliques sur la différenciation de ces cellules organisées magnétiquement sous forme d'agrégats 3D
 
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Alternative Names
Claire Wilhelm researcher

Claire Wilhelm wetenschapper

Languages
French (16)

English (6)