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Infusion of human third-party mesenchymal stromal cells (MSCs) appears to be a promising therapy for acute graft-versus-host disease (aGvHD). To date, little is known about how MSCs interact with the body's innate immune system after clinical infusion. This study shows, that exposure of MSCs to blood type ABO-matched human blood activates the complement system, which triggers complement-mediated lymphoid and myeloid effector cell activation in blood. We found deposition of complement component C3-derived fragments iC3b and C3dg on MSCs and fluid-phase generation of the chemotactic anaphylatoxins C3a and C5a. MSCs bound low amounts of immunoglobulins and lacked expression of complement regulatory proteins MCP (CD46) and DAF (CD55), but were protected from complement lysis via expression of protectin (CD59). Cell-surface-opsonization and anaphylatoxin-formation triggered complement receptor 3 (CD11b/CD18)-mediated effector cell activation in blood. The complement-activating properties of individual MSCs were furthermore correlated with their potency to inhibit PBMC-proliferation in vitro, and both effector cell activation and the immunosuppressive effect could be blocked either by using complement inhibitor Compstatin or by depletion of CD14/CD11b-high myeloid effector cells from mixed lymphocyte reactions. Our study demonstrates for the first time a major role of the complement system in governing the immunomodulatory activity of MSCs and elucidates how complement activation mediates the interaction with other immune cells.

Le recueil des Moralités légendaires constitue un objet d’étude de choix lorsqu’on s’intéresse à la manipulation d’unités narratives préconstruites. Nous nous proposons d’analyser la manière dont Laforgue y exhibe les ficelles de la narration, en les désignant à l’attention du lecteur comme des « poncifs », terme qu’il conviendra de définir avec précision. Par cette configuration fondamentale, l’écriture laforguienne sollicite fortement la relation entre narrateur et narrataire tout comme elle interroge en profondeur les modèles génériques et l’horizon d’attente du destinataire.

À travers une approche territoriale menée dans l’agglomération dunkerquoise où sont concentrés pas moins de 14 sites industriels classés SEVESO, nous avons réalisé une étude des outils de gouvernance locale intervenant dans la gestion des risques et pollutions industriels. Nous avons interrogé les formes d’interaction entre les acteurs (entreprises, représentants de la société civile, acteurs institutionnels) et structures (SPPPI, CLIC, CLI…) concernés par ces risques afin de mettre en évidence les modalités de gouvernance à l’œuvre. Comment les acteurs locaux s’organisent-ils pour vivre et se prémunir dans un environnement pollué par les rejets industriels et exposé aux risques ? Qui participe aux modes de gestion institutionnels, dans quelles structures ? Comment les différentes structures de concertation coexistent-elles et comment se structurent leurs interventions dans la gouvernance locale ? Pour répondre à ces questionnements, une analyse des instances de concertation a été réalisée au moyen d’entretiens qualitatifs menés auprès des acteurs locaux y participant. Les entretiens laissent notamment apparaître des attitudes ambiguës à l’égard des structures de concertation implantées sur le territoire. Bien que les participants critiquent les modalités de fonctionnement de ces dispositifs et leur absence de pouvoir décisionnel, le jeu de la concertation pratiqué dans ces instances semble pourtant accepté de tous, chacun y trouvant un intérêt stratégique. Au-delà de la mise en évidence d’une grande asymétrie des rôles et de la légitimité des acteurs, cette analyse des structures de concertation nous livre également une double lecture du jeu des acteurs locaux « multipositionnés » dans des réseaux formels et informels de relations dans lesquels se définissent les règles de la gouvernance locale.

Background and Objectives Mesenchymal stromal cells (MSC) may be used in cellular therapy to treat graft-versus-host-disease and autoimmune disorders, and in regenerative medicine. Preliminary data suggest limited cellular allogeneic rejection, but less is known about humoral responses. The objective of this study was to investigate whether antibodies against MSC were present after hematopoietic stem cell transplantation (HSCT) including treatment with HLA matched or mismatched allogeneic MSC.Design and Methods Twelve patients were evaluated using flow cytometric cross matches (FCXM) and enzyme-linked immunosorbent assays. Expression of blood group antigens, regarded as alloantigens giving rise to humoral alloimmunity, on MSC were explored using flow cytometry and immunofluorescence.Results Three of 12 patients exhibited late positivity in the FCXM. In absorption studies, antibodies directed against fetal calf serum (FCS), a component of the MSC culture medium, were identified. Healthy individuals expressed varying levels of anti-FCS antibodies and the same pattern was seen in immunosuppressed HSCT patients. MSC did not express blood group antigens. The patients with positive FCXM are alive and well.Interpretation and Conclusions We have shown that immunosuppressed patients can exhibit anti-FCS antibodies, but no alloantibodies, which may bind to MSC. These antibodies seem clinically insignificant.

BackgroundPathological accumulation of cholesterol in late endosomes is observed in lysosomal storage diseases such as Niemann-Pick type C. We here analyzed the effects of cholesterol accumulation in NPC cells, or as phenocopied by the drug U18666A, on late endosomes membrane organization and dynamics.Methodology/principal findingsCholesterol accumulation did not lead to an increase in the raft to non-raft membrane ratio as anticipated. Strikingly, we observed a 2-3 fold increase in the size of the compartment. Most importantly, properties and dynamics of late endosomal intralumenal vesicles were altered as revealed by reduced late endosomal vacuolation induced by the mutant pore-forming toxin ASSP, reduced intoxication by the anthrax lethal toxin and inhibition of infection by the Vesicular Stomatitis Virus.Conclusions/significanceThese results suggest that back fusion of intralumenal vesicles with the limiting membrane of late endosomes is dramatically perturbed upon cholesterol accumulation.

Background: Mesenchymal stromal cells (MSC) have been under investigation for a number of therapies and have lately been in focus as immunosuppressive actors in the field of transplantation. Herein we have extended our previously published in vitro model of MSC-islets in an experimental setting of islet transplantation to the abdominal muscle. Human islets coated with luciferase-GFP transduced human MSC were transplanted to the abdomen muscle tissue of NOD-scid ILR2γnull mice and cellular interactions were investigated by confocal microscopy. Result: The MSC reduced fibrotic encapsulation and facilitated endothelial cell interactions. In particular, we show a decreased fraction of αSMA expressing fibrotic tissue surrounding the graft in presence of MSC-islets compared to islets solely distributed into the muscle tissue. Also, in the presence of MSC, human islet endothelial cells migrated from the center of the graft out into the surrounding tissue forming chimeric blood vessels with recipient endothelial cells. Further, in the graft periphery, MSC were seen interacting with infiltrating macrophages. Conclusion: Here, in our experimental in vivo model of composite human islets and luciferase-GFP-transduced human MSC, we enable the visualization of close interactions between the MSC and the surrounding tissue. In this model of transplantation the MSC contribute to reduced fibrosis and increased islet endothelial cell migration. Furthermore, the MSC interact with the recipient vasculature and infiltrating macrophages.

This article is concentrated on the first texts of Merleau-Ponty. It tries to make clear that there is a bodily origin of the culture. It doesn't involve that we are dealing with a biological anthropology of cultural forms. This article can be read as an attempt to show the different expressions of the body and to reveal a new conception of history.