Encapsulation d'hépatocytes dans un biomatériau poreux en vue d'une implantation dans un modèle animal

Pour pallier le manque de solutions thérapeutiques et le faible nombre de greffons hépatiques disponibles pour traiter certaines atteintes du foie, l ingénierie tissulaire et l implantation de tissus reconstruits représentent des solutions potentielles à explorer. Notre approche repose sur la microencapsulation de cellules hépatiques humaines dans des billes d alginate poreuses. Dans un premier temps, ce travail de thèse a permis de mettre en place de nouvelles combinaisons de matériaux a partir de l alginate et d analyser l influence de ces matériaux sur le comportement mécanique des billes et sur le comportement cellulaire de la lignée HepG2 C3A. La conclusion de cette étude montre que l ajout de collagène et/ou de coating de poly-L-lysine augmente la rigidité des billes et diminue les coefficients de transfert à l intérieur de la bille, tout en permettant une prolifération et un maintien de la fonctionnalité des cellules HepG2 C3A. Ensuite, à titre préliminaire, les billes ont été implantées chez un modèle de souris immunocompétente afin d évaluer la biocompatibilité des matériaux. Dans un deuxième temps, les hépatocytes humains primaires ont été encapsulés dans des billes d alginate mélangées ou non avec du collagène de type I et mis en culture sur des durées de 7 a 14 jours. Les résultats montrent une perte du niveau basal des expressions et des activités des cytochromes P450 3A4 et 1A1, de la fonctionnalité et de la différenciation des hépatocytes en culture statique. Dans un dernier temps, les hépatocytes humains primaires encapsules ont été mis en culture dans deux types de bioréacteurs afin d étudier l effet de la culture en condition dynamique. Les résultats montrent que la culture dynamique en lit fluidise permet d augmenter la fonctionnalité et la différenciation des hépatocytes encapsules. Cette méthode de culture pourrait donc être employée avant l implantation des hépatocytes microencapsulés, afin d assurer une viabilité optimale et un maintien des fonctions métaboliques indispensables dans un contexte de suppléance hépatique.Further to the lack of therapeutic solutions and the low number of hepatic transplants available to treat some hepatic diseases, tissue engineering and implantation of reconstructed tissue are possible alternatives to explore. Our approach is based on microencapsulation of hepatic cells in porous alginate beads. In a first time, this thesis work allowed to set up new combinations of materials based on alginate and to analyze their influence on bead mechanical behavior and on HepG2 C3A behavior. The results of this study shown that the adding of collagen and/or of poly-L-lysine coating increased the rigidity of the beads and decreased the mass transfer coefficients inside the bead while allowing a proliferation and a preservation of the functionality of HepG2 C3A. Then, the beads were implanted in small animal model of immunocompetent mice to estimate the biocompatibility of the different materials. In a second time, the primary human hepatocytes were encapsulated in beads of alginate mixed or not with type I collagen and cultivated during 7 to 14 days. The results have shown a basal loss of the level of the expressions and the activities of cytochromes P450 3A4 and 1A1, the functionality and the differentiation of encapsulated primary human hepatocytes. In a last time, encapsulated primary human hepatocytes were cultivated in two types of bioreactors in order to analyze the effect of dynamic culture conditions. The datas shown that the dynamic culture in fluidized bed bioreactor enhanced the functionality and the differentiation of encapsulated hepatocytes. This culture condition could be used before implantation of encapsulated hepatocytes in order to assure an optimal viability and a good maintenance of metabolic functions essential in a context of hepatic suppliance.COMPIEGNE-BU (601592101) / SudocSudocFranceF

Management of Acute Demyelinating Attacks in the Pediatric Population: A Swiss Consensus Statement.

Abstract: Background and methods: Acquired demyelinating syndromes (ADS) encompass distinct entities and occur in approximately 1/100,000 children. While the use of high dose intravenous corticosteroids is well-established, agreement on steroid taper and type of second line therapy is lacking. A comprehensive, unified and standardized treatment approach is crucial in the management of patients with rare diseases. Therefore, this study performed from July 2018 to June 2020 aimed at developing a national consensus on the management of ADS in the pediatric population using the Delphi approach. Consensus was defined as agreement in >75%. Designated Neuropediatricians with an expertise in the management of pediatric neuroinflammatory diseases in all university and cantonal hospitals of Switzerland were included. The response rate was 100%. Results: High-dose i.v. methylprednisolone (20–30 mg/kg/die for 5 days) is the first line treatment irrespective of the distinct entity of the ADS. An oral steroid taper is recommended in acute demyelinating encephalomyelitis (ADEM) and in neuromyelitis optica spectrum disorder (NMO-SD). However, in the latter more in the sense of bridging. The choice of second line treatment depends on the entity of ADS: in optic neuritis (ON) and ADS due to relapsing remitting multiple sclerosis, first line treatment should be repeated, whereas plasma exchange is recommended in NMO-SD, ADEM and transverse myelitis. Conclusions: A national guideline allowing for a more unified approach in the management of pediatric ADS will enhance future research in this field, making data more comparable. The definition of inadequate treatment response to first line therapy remains a challenge and requires future research

Epidemiology of metastatic castration-resistant prostate cancer: A first estimate of incidence and prevalence using the French nationwide healthcare database

International audienceBackground: There is a lack of information about the burden of metastatic castration-resistant prostate cancer (mCRPC). The present work aims to estimate the incidence and prevalence of mCRPC in 2014 using the French nationwide healthcare database (SNDS).Methods: Prevalence and incidence were estimated based on an SNDS extraction of men covered by the general healthcare insurance (86 % of the French population), and aged ≥40. Patients with mCRPC were identified amongst prostate cancer cases using an algorithm estimating a date of first metastasis management and a date of castration resistance. This algorithm was validated by clinical experts through a blind review of 200 anonymized medical charts from SNDS data. Prevalence and incidence were standardized on the European Standard Population (2013 edition).Results: Prevalence and incidence of mCRPC were estimated as, respectively, 62 and 21 cases per 100 000 men in 2014. Less than one mCRPC case per 100 000 was observed in men aged 40-49. Maximum mCRPC incidence was in men aged 80-89 (175 per 100 000). The algorithm used for mCRPC identification had 97 % positive and 99 % negative predictive values.Conclusion: The good performances of the algorithm for mCRPC identification and the consistency of the generated results with the existing data highlight the robustness of these first estimates of mCRPC prevalence and incidence. Future updates will call for algorithm adjustment as practices evolve over time. These first real-life data will serve for future follow-up of the impact of changes in the management of prostate cancer

Abiraterone acetate versus docetaxel for metastatic castration-resistant prostate cancer: a cohort study within the French nationwide claims database

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Erratum to ``Measurement of the atmospheric muon flux with a 4 GeV threshold in the ANTARES neutrino telescope'' [Astroparticle Physics 33 (2) (2010) 86-90]

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Time series of oceanographic parameters measured at the Lacaze-Duthiers Canyon (LDC) and the open-sea convection region in the Gulf of Lion (LION) from January 2008 to June 2010.

<p>(<b>a</b>) Potential temperature at 500 and 1,000 m depth at the LDC mooring site and (<b>b</b>) from various water depths at the LION site, jointly with (<b>c</b>) salinity at 2,300 m depth, (<b>d</b>) horizontal current speed and (<b>e</b>) vertical current speed from various water depths at the LION site. The four levels of temperature measurements at LION presented here are a sub-set of measurement depths (see Fig. S1). Essentially stable temperatures in the deepest layers in 2008 show that open-sea convection reached only 700 m and did not modify the deep water in the study area. In contrast, strong convection events, reaching 2,300 m depth, occurred during February-March 2009 and 2010 with an abrupt cooling of the upper water column and an increase in temperature and salinity in the deep layers. A concurrent increase in current speed was also noticed in winter 2009 and 2010. The 5-month long data gap in 2009 is due to a damaging of the mooring line during the April 2009 recovery, which induced a postponement of its redeployment to September 2009.</p

Links between bioluminescence, current speed and the modification of the properties of the Western Mediterranean Deep Water (WMDW).

<p>Box-and-whisker plot of median PMT counting rates (log scale) versus current speed classes for salinities higher (red) or lower (grey) than 38.479 for data recorded in (<b>a</b>) 2008, (<b>b</b>) 2009 and (<b>c</b>) between January and June 2010. The salinity threshold of 38.479 is used as a marker of the intrusion of newly formed deep water at the ANTARES site. While bioluminescence increases with current speed, it is also enhanced by the modification of WMDW (red box-plots). The top and bottom of each box-plot represent 75% (upper quartile) and 25% (lower quartile) of all values, respectively. The horizontal line is the median. The ends of the whiskers represent the 10^th and 90^th percentiles. Outliers are not represented. The statistical comparison between the two box-plots (red and grey) in each current class is given by the Kruskal-Wallis test: the observed difference between the two samples is significant beyond the 0.05 (*), the 0.01 (**) and the 0.001 (***) levels. The absence of an asterisk in some current classes indicates that the difference between the two box-plots is not significant. The number of measurements for salinity lower or higher than 38.479 is given in black or in red, respectively. Note the different scales of figures a, b and c.</p