The role of sulfoglucuronosyl glycosphingolipids in the pathogenesis of monoclonal IgM paraproteinemia and peripheral neuropathy

In IgM paraproteinemia and peripheral neuropathy, IgM M-protein secretion by B cells leads to a T helper cell response, suggesting that it is antibody-mediated autoimmune disease involving carbohydrate epitopes in myelin sheaths. An immune response against sulfoglucuronosyl glycosphingolipids (SGGLs) is presumed to participate in demyelination or axonal degeneration in the peripheral nervous system (PNS). SGGLs contain a 3-sulfoglucuronic acid residue that interacts with anti-myelin-associated glycoprotein (MAG) and the monoclonal antibody anti-HNK-1. Immunization of animals with sulfoglucuronosyl paragloboside (SGPG) induced anti-SGPG antibodies and sensory neuropathy, which closely resembles the human disease. These animal models might help to understand the disease mechanism and lead to more specific therapeutic strategies. In an in vitro study, destruction or malfunction of the blood-nerve barrier (BNB) was found, resulting in the leakage of circulating antibodies into the PNS parenchyma, which may be considered as the initial key step for development of disease

Ultra sensitive biosensor based on impedance spectroscopy at microwave frequencies for cell scale analysis

International audienceThis paper presents an original approach for biological cell discrimination using impedance spectroscopy analysis at microwave frequencies. The proposed method allows label-free analysis at the cell scale using high frequency electromagnetic waves as a non-invasive probe to analyze the intracellular medium. In the present case, the biosensor design takes advantage of classical planar microwave filter topology, where coupling zones present high sensitivity to tiny dielectric perturbations. With proper design, these specific areas can be used as an electromagnetic (EM) detector. In the present work, biosensor sensitivity allows reaching selective biological sample detection and bio-impedance measurements down to single-cell analysis. As presented in this paper, this concept has been experimentally validated with characterisations conducted on biological cancerous stem cells (cells considered at a low differentiation degree) and U87 glial cells (differentiated cells); both coming from human nervous system. Stem cells are almost similar in shape and size as differentiated cells. They are therefore quite difficult to identify using a microscope, and studies focusing on their differentiation mechanisms are very challenging. Cell chemical labeling would have been suitable if we would have been sure that used label will not induce an unwanted cell differentiation. To the contrary, EM impedance measurements show a significant difference between stem and differentiated cells dielectric permittivity. Therefore, such measurements can be an efficient approach to determine cell differentiation degree in a non-invasive way. As a label-free approach, the high frequency impedance spectroscopy could be very interesting for accurate discrimination of un-differentiated cells. Indeed, stem cells are currently the subject of a large research effort in the biologist community; especially in case of cancers, where cancerous stem cells are suspected to be the origin of most of tumor recurrences. Hence, based on this identification technique, a new diagnostic analysis could be developed for early cancer recurrence prevention

Fibroblaste adventitiel, un acteur important de l’artérite à cellules géantes

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UHF dielectrophoretic handling of individual biological cells using BiCMOS microfluidic RF-sensors

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SUMCASTEC_190426_NA_PLUMEE19_Conference paper_.pdf_Limoges_T. Provent_Public_NA

Paper entitled "Continuous Cell Sorting by High Frequencies Dielectrophoresis" for the PLUMEE 2019 conference: the French speaking Multidisciplinary conference on Material, Environment and Electronic, April 10-12th, Limoges, France

Discrimination of Glioblastoma Cancer Stem Cells by measuring their UHF-Dielectrophoresis Crossover Frequency

International audienceThis paper introduces firsts results of characterization of glioblastoma cell lines; measuring their crossover frequencies by dielectrophoresis (DEP) technics in the UHF frequency range (above 50 MHz). LN18 line cells were cultured following different conditions, in order to achieve an enrichment of cancer stem cells (CSCs). The DEP electrokinetic method is used to discriminate the CSCs from the differentiated cells. In this study, microfluidic lab-on-chip systems implemented on Bipolar-Complementary Oxide Semiconductor (BiCMOS) technology is used allowing single cell handling and analysis. Based on measurements of their own intracellular specificities, the enriched CSCs population, cultured in dedicated defined medium, have shown clear differences of DEP crossover frequency signatures compared to differentiated cells cultured in normal medium. That demonstrates the concept and validates the technique efficiency for CSC discrimination in glioblastoma pathology