Erythroid Promoter Confines FGF2 Expression to the Marrow after Hematopoietic Stem Cell Gene Therapy and Leads to Enhanced Endosteal Bone Formation

Fibroblast growth factor-2 (FGF2) has been demonstrated to be a promising osteogenic factor for treating osteoporosis. Our earlier study shows that transplantation of mouse Sca-1+ hematopoietic stem/progenitor cells that are engineered to express a modified FGF2 leads to considerable endosteal/trabecular bone formation, but it also induces adverse effects like hypocalemia and osteomalacia. Here we report that the use of an erythroid specific promoter, β-globin, leads to a 5-fold decrease in the ratio of serum FGF2 to the FGF2 expression in the marrow cavity when compared to the use of a ubiquitous promoter spleen focus-forming virus (SFFV). The confined FGF2 expression promotes considerable trabeculae bone formation in endosteum and does not yield anemia and osteomalacia. The avoidance of anemia in the mice that received Sca1+ cells transduced with FGF2 driven by the β-globin promoter is likely due to attenuation of high-level serum FGF2-mediated stem cell mobilization observed in the SFFV-FGF2 animals. The prevention of osteomalacia is associated with substantially reduced serum Fgf23/hypophosphatemia, and less pronounced secondary hyperparathyroidism. Our improved stem cell gene therapy strategy represents one step closer to FGF2-based clinical therapy for systemic skeletal augmentation

Système de nettoyage ultrasonore à grande échelle : Distribution acoustique dans un dispositif multi-transducteurs

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Characterization of the activity of ultrasound emitted in a perpendicular liquid flow using Particle Image Velocimetry (PIV) and electrochemical mass transfer measurements

International audienceThe present work is dedicated to the study of the interactions between a liquid circulation and a perpendicular acoustic wave propagation. A specific experimental setup was designed to study one transducer operating at 20 kHz, with the help of electrochemical mass transfer measurements combined with Particle Image Velocimetry (PIV) determination. Electrodes were located on the wall opposite to the acoustic emission. Experiments were performed for various Reynolds numbers: from 0 to 21700 (different liquid flow rates and viscosities). Both PIV and electrochemical measurements methods were found to be relevant, and had delivered complementary information. Even if PIV showed that the plume due to streaming was highly deflected by the additional flow, electrochemical measurements showed that there was still an activity, higher than in silent conditions, on the wall facing the transducer. Thus the ultrasound contribution remained noticeable on the surface opposite to the transducer even for a disturbed hydrodynamic environment due to the presence of a liquid circulation perpendicular to the wave propagation

Conception d'une chambre de diffraction RX haute température pour l'étude de l'adsorption d'un gaz par un solide sous haute pression

Le caractère original et innovateur de la chambre d'analyse qui est présentée dans ce travail repose sur son champ d'utilisation large, en particulier dans le domaine de l'adsorption sous haute pression d'un gaz condensable. Cette chambre qui a été spécialement conçue au Laboratoire de Recherches sur la Réactivité des Solides de l'Université de Bourgogne est susceptible d'opérer dans des domaines étendus de pression et de température, respectivement (10-4-104) hPa et (20 - 350) °C. Un doigt de gant en béryllium monté sur un passage électrique assure l'étanchéité de l'enceinte réactionnelle ; l'échantillon est chauffé par conduction. La chambre qui est placée dans une enceinte externe (équipée d'une fenêtre hémi-cylindrique en kapton) maintenue sous un vide dynamique de 10-4 hPa pour s'affranchir de toute oxydation du béryllium et de toutes émanations éventuelles de gaz condensable est installée sur un goniomètre à axe horizontal muni d'un compteur à localisation courbe INEL CPS 120. L'ensemble du dispositif est connecté d'une part à une ligne de vide, d'autre part à une réserve de gaz. Un exemple d'utilisation de la chambre est présenté dans le cas de l'adsorption et la désorption sous 5 x 103 hPa de l'isopentane par la zéolite 5A.The originality of the present new X-ray reactor chamber is based on its wide range of use for studying solid-gas reactions, especially for condensable gases under high pressure. This chamber constructed in the Laboratory of Research on the Reactivity of Solids of the University of Burgundy, permits studies at wide pressure and temperature ranges from 10-4 hPa to 104 hPa and from room temperature to 350 °C respectively. A beryllium tube mounted on a feedthrough ensures the tightness of the reactor chamber. The sample is heated by conduction. The chamber which is set into an external tight container is fixed on an horizontal axis goniometer connected to a curved X ray position sensitive detector INEL CPS 120. During the experiments a continuous vacuum of approximately 10-4 is imposed into the external container equiped with a semi-cylindrical kapton window, to prevent any oxidation of beryllium and any casual outflow of the condensable gas. The X-ray reactor chamber is connected on one side to vacuum and on the other side to a gas reserve. One application of the X-ray reactor chamber is shown from the study of the adsorption and desorption of isopentane on a zeolite 5A under 5 x 103 hPa