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

Grafts of olfactory stem cells restore breathing and motor functions after a rat spinal cord injury

International audienceThe transplantation of Olfactory Ecto-Mesenchymal Stem Cells (OEMSCs) could be a helpful therapeutic strategy for spinal cord repair. Using an acute rat model of high cervical contusion that provokes a persistent hemi-diaphragmatic and foreleg paralysis, we evaluated the therapeutic effect of a delayed syngeneic transplantation (two days post-contusion) of OEMSCs within the injured spinal cord. Respiratory function was assessed using diaphragmatic electromyography and neuro-electrophysiological recordings of phrenic nerves (innervating the diaphragm). Locomotor function was evaluated using the ladder-walking locomotor test. Cellular reorganization in the injured area was also studied using immunohistochemical and microscopic techniques. We report a substantial improvement in breathing movements, in activities of the ipsilateral phrenic nerve and ipsilateral diaphragm and also in locomotor abilities four months post-transplantation with nasal OEMSCs. Moreover, in the grafted spinal cord, lesioned areas and inflammation were reduced. Some grafted stem cells adopted a neuronal phenotype and axogenesis was observed in the injury site. The therapeutic effect on the supraspinal command is presumably due to both neuronal replacements and beneficial paracrine effects on the injury area. Our study provides evidence that nasal OEMSCs could be a first step in clinical application, particularly in patients with reduced breathing/locomotor movements

Syngeneic Transplantation of Olfactory Ectomesenchymal Stem Cells Restores Learning and Memory Abilities in a Rat Model of Global Cerebral Ischemia

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Imaging Spectrometry of Inland and Coastal Waters: State of the Art, Achievements and Perspectives

Imaging spectrometry of non-oceanic aquatic ecosystems has been in development since the late 1980s when the first airborne hyperspectral sensors were deployed over lakes. Most water quality management applications were, however, developed using multispectral mid-spatial resolution satellites or coarse spatial resolution ocean colour satellites till now. This situation is about to change with a suite of upcoming imaging spectrometers being deployed from experimental satellites or from the International Space Station. We review the science of developing applications for inland and coastal aquatic ecosystems that often are a mixture of optically shallow and optically deep waters, with gradients of clear to turbid and oligotrophic to hypertrophic productive waters and with varying bottom visibility with and without macrophytes, macro-algae, benthic micro-algae or corals. As the spaceborne, airborne and in situ optical sensors become increasingly available and appropriate for aquatic ecosystem detection, monitoring and assessment, the science-based applications will need to be further developed to an operational level. The Earth Observation-derived information products will range from more accurate estimates of turbidity and transparency measures, chlorophyll, suspended matter and coloured dissolved organic matter concentration, to more sophisticated products such as particle size distributions, phytoplankton functional types or distinguishing sources of suspended and coloured dissolved matter, estimating water depth and mapping types of heterogeneous substrates. We provide an overview of past science, current state of the art and future directions so that early career scientists as well as aquatic ecosystem managers and associated industry groups may be prepared for the imminent deluge of imaging spectrometry data

Decreased darunavir concentrations during once-daily co-administration with maraviroc and raltegravir: OPTIPRIM-ANRS 147 trial

International audienceBackgroundThe OPTIPRIM-ANRS 147 trial compared intensive combination ART (darunavir/ritonavir, tenofovir disoproxil fumarate/emtricitabine, raltegravir and maraviroc) started early during primary HIV-1 infection with standard tritherapy with darunavir/ritonavir, tenofovir disoproxil fumarate and emtricitabine. From month 6 to 18, the percentage of viral load values <50 copies/mL was lower in the pentatherapy arm than in the tritherapy arm. Here we compared antiretroviral drug concentrations between the two arms.MethodsPlasma samples were collected from 50 patients at various times after drug administration. A Bayesian approach based on published population pharmacokinetic models was used to estimate residual drug concentrations (Ctrough) and exposures (AUC) in each patient. A mixed linear regression model was then used to compare the AUC and Ctrough values of each drug used in both groups.ResultsPublished models adequately described our data and could be used to predict Ctrough and AUC. No significant difference in tenofovir disoproxil fumarate, emtricitabine and ritonavir parameters was found between the two arms. However, darunavir Ctrough and AUC were significantly lower in the pentatherapy arm than in the tritherapy arm (P = 0.03 and P = 0.04, respectively).ConclusionsAdding maraviroc and raltegravir to darunavir-based tritherapy decreased darunavir concentrations. Compliance issues, maraviroc–darunavir interaction and raltegravir–darunavir interaction were suspected and may affect the kinetics of viral decay during pentatherapy. A specific pharmacokinetic interaction study is needed to explore the interactions between darunavir and maraviroc and raltegravir