Olfactory ecto-mesenchymal stem cells in regenerative medicine : therapeutic potential from bench to bedside

L’absence de traitements efficaces pour régénérer l’encéphale a orienté les recherches vers un nouveau domaine : la thérapie cellulaire. Dans ce contexte, les cellules souches apparaissent comme un outil de choix pour reformer le tissu cérébral et restaurer les capacités cognitives et les cellules souches olfactives ecto-mésenchymateuses (CSOE-Ms), localisées dans la cavité nasale, apparaissent comme un candidat idéal. Chez des rats, nous avons démontré que la transplantation de CSOE-Ms restaurait les capacités mnésiques impactées après une ischémie et entraînait une augmentation de la neurogenèse dans l’hippocampe.Nous avons ensuite promu l’intérêt de ces cellules auprès de la communauté scientifique et du monde vétérinaire en caractérisant les cellules de huit espèces d’intérêt. Ces travaux ont révélé de fortes similitudes entre les cellules de toutes les espèces, ce qui permet de généraliser en partie les propriétés thérapeutiques de ces cellules depuis les données obtenues majoritairement à partir de cellules humaines. Afin de confirmer ces observations in vitro, nous avons effectué des greffes dans le quatrième ventricule cérébral de vieux chiens présentant un syndrome dégénératif lié au vieillissement. L’injection de cellules souches a permis de restaurer en partie les capacités cognitives perturbées et s’est révélé sans aucun effet délétère.Les résultats obtenus au cours de cette thèse confirment l’intérêt des CSOE-Ms pour traiter les atteintes du système nerveux central et suggèrent qu’elles pourraient être un outil majeur pour la médecine régénérative.The lack of effective treatments to regenerate the brain led research into a new field: the cellular therapy. In this context, stem cells appear as a tool of choice to regenerate brain tissues and restore cognitive abilities. Olfactory ecto-mesenchymal stem cells (OE-MSCs), located in the nasal cavity, appear as an ideal candidate.In rats, we have demonstrated that transplantation of OE-MSCs restored memory capacities affected after ischemia and led to an increase in neurogenesis within the hippocampus.We then promoted the interest of these cells toward the scientific and veterinary community by characterizing the cells of eight species of interest. This work revealed strong similarities between the cells of all the species, which makes it possible to generalize in part their therapeutic properties from the data obtained mainly from human cells.To confirm these observations in vitro, we performed transplants in the fourth cerebral ventricle of old dogs with degenerative syndrome related to aging. The injection of stem cells partially restored disturbed cognitive abilities and was shown to have no deleterious effect.The results obtained during this thesis confirm the interest of OE-MSCs to treat central nervous system injuries and suggest that they could be a major tool for regenerative medicine

Context-aware cognitive design assistant: Implementation and study of design rules recommendations

Design rules are an essential interface to facilitate the information exchange between designers and experts. Despite many innovations in Knowledge-Based Engineering and Knowledge Management, unstructured design rules documents are still widely used in the manufacturing industry. Due to the complexity of the design process, these documents often contain hundreds of design rules, applicable in varying design contexts. Searching for the right rules according to a design context is demanding in time and cognitive resources. In this paper, we propose a Context-Aware Cognitive Design Assistant (CACDA) to capture the design context and perform tasks such as the recommendation of design rules, the verification of design solutions, or the automation of design routines. Contrary to existing works in model quality testing, the CACDA uses a proactive approach of design rules application and helps designers to provide error-free designs on first attempt. In this paper, we present the design rules recommendation system of the CACDA, its capabilities and its implementation. Then, to measure the impact of design rules recommendations on the design process, we compare our approach with the use of traditional design rules documents. Results show that the use of the CACDA’s design rules recommendations lower the perceived difficulty of design rules retrieval from 75 to 43.5 on a scale of 100. On average, participants that used the demonstrator successfully applied 8.6 design rules on the 25 applicable design rules of our set. Participants that used unstructured documentation correctly applied 4.3 design rules. The global cognitive weight of the design activity as well as the design rules retrieval performances appear to be unchanged. These results demonstrate the usability of the demonstrator and show a positive impact on the design process and on the quality of CAD models. Future works will focus on the overcome of the main limitations of our current experiments, with a panel of professional designers, a lager design rules set and the implementation of several lacking features of the CACDA into the demonstrator.Capgemini DEM

Histone H1 of Saccharomyces cerevisiae Inhibits Transcriptional Silencing

Eukaryotic genomes contain euchromatic regions, which are transcriptionally active, and heterochromatic regions, which are repressed. These domains are separated by “barrier elements”: DNA sequences that protect euchromatic regions from encroachment by neighboring heterochromatin. To identify proteins that play a role in the function of barrier elements we have carried out a screen in S. cerevisiae. We recovered the gene HHO1, which encodes the yeast ortholog of histone H1, as a high-copy modifier of barrier activity. Histone H1 is a linker histone that binds the outside of nucleosomes and modifies chromatin dynamics. Here we show that Hho1p reinforces the action of several types of barrier elements, and also inhibits silencing on its own

Evaluation de la contamination des mollusques bivalves vivants et des produits de la pêche prélevés au stade de la distribution en France par des vibrio potentiellement entéropathogènes

Introduction et objectifs Les vibrions, bactéries de la famille des Vibrionaceae, sont présents naturellement dans les eaux côtières et estuariennes du monde entier et chez de nombreuses espèces de coquillages et de crustacés fréquemment consommés en France. Certaines espèces (Vibrio parahaemolyticus, Vibrio vulnificus et Vibrio cholerae nonO1/non-O139) peuvent induire des phénomènes pathologiques chez l’Homme suite à la consommation de produits de la mer crus, insuffisamment cuits ou contaminés après cuisson. Le plan exploratoire mis en œuvre en 2019 par la Direction générale de l’Alimentation du ministère de l’Agriculture et de l’Alimentation avait pour objectif d’estimer la contamination de produits de la mer prélevés au stade de la distribution en France par ces trois espèces de Vibrio potentiellement entéropathogènes et par conséquent l’exposition potentielle des consommateurs. Matériels et méthodes Des prélèvements de mollusques bivalves vivants et de produits de la pêche ont été réalisés au stade de la distribution. La répartition des échantillons dans les treize régions métropolitaines a été définie proportionnellement à la densité de population humaine présente dans chaque région. La contamination des échantillons a été déterminée selon la méthode décrite dans la norme ISO 21872-1:2017. Résultats, discussion et conclusion Parmi les 92 échantillons de coquillages vivants et les 95 échantillons de produits de la pêche crus ou cuits analysés, seuls des produits crus (moules, huîtres (n=59) et crevettes (n=6)) étaient contaminés par V. parahaemolyticus, V. vulnificus et/ou V. cholerae. Des souches V. parahaemolyticus potentiellement entéropathogènes (présence de tdh et/ou trh) ont été isolées de moules (n=5) et d’huîtres (n=10). L’ensemble des résultats obtenus dans cette étude exploratoire montre que l’état du produit (cru ou cuit) pourrait avoir un impact important sur la présence des Vibrio potentiellement entéropathogènes. Dans le futur, il sera essentiel d’évaluer les niveaux de contamination de tels produits afin de mieux estimer le risque pour le consommateur

A unique method for the isolation of nasal olfactory stem cells in living rats

International audienceStem cells are attractive tools to develop new therapeutic strategies for a variety of disorders. While ethical and technical issues, associated with embryonic, fetal and neural stem cells, limit the translation to clinical applications, the nasal stem cells identified in the human olfactory mucosa stand as a promising candidate for stem cell-based therapies. Located in the back of the nose, this multipotent stem cell type is readily accessible in humans, a feature that makes these cells highly suitable for the development of autologous cell-based therapies. However, preclinical studies based on autologous transplantation of rodent olfactory stem cells are impeded because of the narrow opening of the nasal cavity. In this study, we report the development of a unique method permitting to quickly and safely biopsy olfactory mucosa in rats. Using this newly developed technique, rat stem cells expressing the stem cell marker Nestin were successfully isolated without requiring the sacrifice of the donor animal. As an evidence of the self-renewal capacity of the isolated cells, several millions of rat cells were amplified from a single biopsy within four weeks. Using an olfactory discrimination test, we additionally showed that this novel biopsy method does not affect the sense of smell and the learning and memory abilities of the operated animals. This study describes for the first time a methodology allowing the derivation of rat nasal cells in a way that is suitable for studying the effects of autologous transplantation of any cell type present in the olfactory mucosa in a wide variety of rat models

Immuncompetence of brown and brook trouts living in different subantarctic freshwaters ecosystems

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The ecotoxicological risk in sub-Antarctic regions : PCBs and organochlorine pesticides contamination of trout from Kerguelen Islands (48° 35'S-49° 54'S and 68° 43'E-70° 35'E)

International audienceThe polar and subpolar ecosystems receive persistent organic pollutants (POP) by atmospheric transfer. PCBs (polychlorinated biphenyls) and other ubiquitous organochlorines were detected from the late sixties. In subpolar areas, the snow acts as a dynamic reservoir. A multidisciplinary study funded by the French National Research Agency (ANR Risker program) in collaboration with the French Polar Institute (Immunotoxker program 409) began in 2009 to participate in the assessment of the global contamination, among others. In this objective, the Kerguelen Islands constitute a model of area not directly exposed to industrial, agricultural or urban pollution. This archipelago in the Southern Ocean possesses a complex hydrological network, with an ichthyofauna composed of salmonids introduced in the fifties. This first study relates to the contamination of trout (Salmo trutta) with organochlorine pollutants. These chemicals were widely used for over 50 years and are highly persistent and responsible for (eco)toxicological concerns. Also, the bioaccumulation assessment is concomitant to the measurement of hepatic enzymatic biomarkers involved in biotransformation process and protection against oxidative stress. The PCBs bioaccumulation shows a large heterogeneity, which results in average concentrations close to 250 ng per g dry weight, including optimal values in some individuals, reaching 5 micro g.g-1 dw. Moreover, we describe seasonal variations, with contamination level increased during summer, and inter-site differences in connection with the habitat. So, trout from the lake ecosystems are more impacted than river fish. Furthermore, lower levels of organochlorine pesticides were detected. The liver biomarkers respond to the contamination by a large variability. However statistical correlations indicate a relationship between biomarkers and bioaccumulation, particularly between the liver catalase and the concentration of prioritary PCBs, suggesting an immunotoxic effect. The continuation of the program will be devoted to the search of integrative indicators, associated to the measurement of immunotoxic and reprotoxic alterations in Kerguelen's trou

Immuno-écologie des populations de salmonidés des îles Kerguelen (Terres Australes Françaises)

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