Cholecystokinin (CCK) secreting enteroendocrine (EEC) I cells which distribute in gastrointestinal tract play an important role in lipid sensing, digestion and fatty acids uptake. Although a lot of research has been performed, the whole mechanism of fat sensing and fatty acid uptake and hormone expression in the CCK cells is still unclear. Global analysis to characterise the CCK cells is essential. CCK cells have an indistinct morphology, a diffuse distribution and a small percentage of population in the small intestine. However, the generation of genetic fluorescence tagged animal model facilitates the study of these cells. In this thesis, single cell dissociation methods and RT-PCR methodologies for detecting nutrient sensing receptors and fatty acids transporters were established and optimised. Expression of mRNAs for fat sensing GPCRs were detected in mouse duodenal epithelium. Expression of FATP family and CD36 in CCK cells and enterocytes was studied by RT-PCR. FATP2, FATP4 and CD36 mRNA were found in both CCK cells and enterocytes. Cell culture methodologies enabling the study of function (calcium imaging and FACS analysis) were established and optimised by checking the cell viability as a criterion. The methodology combining the immunochemistry and FACS analysis to study the hormone was established but requires further optimisation.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23088号 / 医博第4715号 / 新制||医||1050(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 柳田 素子, 教授 岩田 想, 教授 浅野 雅秀 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Les travaux de recherche menés dans cette thèse s’inscrivent dans le cadre de la réalisation de la technologie cellule solaire intégrée (i-Cell), qui est une technologie innovante de fabrication de cellules solaires à hauts rendements de conversion et à bas coût de production. L’i-Cell consiste en la réalisation de plusieurs cellules élémentaires ou sous-cellules, en feuilles minces de silicium cristallin purifié, qui sont connectées en série sur un substrat de Si fritté bas coût. La technologie i-Cell permet en effet la réduction du coût de la plaquette grâce à la faible épaisseur des feuilles de silicium et grâce à l’utilisation de substrats issus du frittage de poudres de silicium. Dans une telle structure la fonction photovoltaïque est assurée par la feuille mince de surface alors que le transport du courant et la fonction mécanique sont gérés par le substrat fritté ce quipermet de réduire les coûts de fabrication de la cellule. En effet, à l’instar des couches minces, on peut décomposer la couche active en cellules de faibles surfaces et ainsi produire sur une surface standard (156 x 156 mm²), une cellule dans laquelle circule un faible courant qui permet de réduire fortement la consommation des métaux précieux au sein de la cellule (Argent) et entre les cellules du module (Cuivre). En outre, la configuration des cellules à i-Cell permet de s’affranchir des busbars en Ag traditionnellement utilisés dans les technologies silicium. Ceci présente l’avantage d’éviter le masquage de la lumière et donc d'augmenter la puissance de la cellule. Ce travail de thèse s’articule sur deux axes de recherche principaux. Le premier est orienté sur l’étude de la cinétique d’oxydation thermique de substrats de silicium frittés poreux. Le deuxième axe concerne la réalisation du substrat fritté intégré et la réalisation des premiers prototypes d’i-Cells sur ces derniers. Ce travail a permis de démontrer la faisabilité de l’i-Cell et de réaliser des prototypes d’i-Cell sur le substrat fritté intégré. Des rendements de conversion PV supérieurs à 18% ont été ainsi obtenus. / The research work conducted in this thesis are within the framework of the realization of the integrated solar cell technology (i-Cell), which is an innovative solar cell technology with a high conversion efficiency and a low cost production. The i-Cell consists of the realization of several elementary cells or sub-cells, in purified crystalline silicon thin foils, which are connected in series on a low cost sintered silicon substrate. In fact, the i-Cell technology allows the reduction of the cost of the wafer thanks to the low thickness of the silicon foils and through the use of substrates obtained from the sintering silicon powders. In such a structure, the photovoltaic function is provided by the thin purified Si foil on the surface. Whereas both the current transport and the mechanical function are provided by the sintered silicon substrate – thin allows to reduce the cell manufacturing costs. In fact, just like thin films, we can decompose the active layer in small cell surfaces and thus produce, on a standard surface (156 x 156 mm²), a low current cell that greatly reduces the consumption of precious metals within the cell (Silver) and between the cells within the module (Copper). Furthermore, the configuration of cells in the i-Cell technology permits to eliminate the use of Silver busbars traditionally used in the Si solar cell technologies. This offers the advantage of avoiding the masking light and thus increases the power of the i-Cell. This thesis work focuses on two main axes of research: The first axis relates to the study of the kinetics of thermal oxidation of porous sintered silicon substrates. The second axis of research focuses on the realization of the “integrated sintered substrates”, which consists of the realization of local conductive zones on the insulating porous sintered substrate, and the fabrication of the first i-Cells prototypes on them. This work demonstrated the feasibility of i-Cell and produced prototypes of i-Cell on the integrated sintered substrate. High photovoltaic conversion efficiencies, greater than 18%, were obtained.

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We report the use of thin film poly(dimethylsiloxane) (PDMS) prints for the arrayed mass production of highly uniform 3-D human HT29 colon carcinoma spheroids. The spheroids have an organotypic density and, as determined by 3-axis imaging, were genuinely spherical. Critically, the array density impacts growth kinetics and can be tuned to produce spheroids ranging in diameter from 200 to 550 µm. The diffusive limit of competition for media occurred with a pitch of ≥1250 µm and was used for the optimal array-based culture of large, viable spheroids. During sustained culture mass transfer gradients surrounding and within the spheroids are established, and lead to growth cessation, altered expression patterns and the formation of a central secondary necrosis. These features reflect the microenvironment of avascularised tumours, making the array format well suited for the production of model tumours with defined sizes and thus defined spatio-temporal pathophysiological gradients. Experimental windows, before and after the onset of hypoxia, were identified and used with an enzyme activity-based viability assay to measure the chemosensitivity towards irinotecan. Compared to monolayer cultures, a marked reduction in the drug efficacy towards the different spheroid culture states was observed and attributed to cell cycle arrest, the 3-D character, scale and/or hypoxia factors. In summary, spheroid culture using the array format has great potential to support drug discovery and development, as well as tumour biology research. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.