Le mythe de Robinson Crusoé à l’épreuve du monde global : il n’y a pas d’ailleurs. Étude du motif de l’empreinte dans L’empreinte à Crusoé de Patrick Chamoiseau

De quel ailleurs peut bien nous parler la réécriture contemporaine du mythe de Robinson Crusoé par Patrick Chamoiseau, en 2012, alors que la planète est à la fois menacée par les déséquilibres écologiques et engagée dans une mondialisation des échanges ? L’empreinte à Crusoé est le récit sans aventure d’un homme qui, incapable de se souvenir d’où il vient véritablement, comprend qu’il habite un lieu chargé d’ailleurs. Or, c’est à travers l’empreinte de pas découverte sur la plage que se révèle et se recompose l’identité d’Ogomtemêli et sa place dans le monde. Plus qu’une péripétie, l’empreinte est un motif à partir duquel le naufragé devient la conscience historique et écologique de l’humanité vivant sur une seule et même terre, un lieu-monde dans lequel la relation doit supplanter l’exploitation

La représentation du sacré dans Le Roi Pêcheur de Julien Gracq

S’il est tout à fait incontestable que Julien Gracq n’exprime à travers ses œuvres aucune pensée conforme à une doctrine religieuse définie, il n’est pas moins évident que son œuvre revêt un caractère spirituel d’une grande profondeur. Les différents commentateurs de l’œuvre de Gracq se sont souvent appuyés sur une remarque de l’auteur lors d’un entretien avec Jean Carrière : Je ne crois pas avoir l’esprit religieux : les questions qui passent pour obséder les esprits de ce genre, je ne me le..

Impact of Femoral Ossification on Local and Systemic Cardiovascular Patients' Condition

International audienceBackground: Vascular calcifications are associated with a high cardiovascular morbi-mortality in the coronary territory. In parallel, femoral arteries are more calcified and develop osteoid metaplasia (OM). This study was conducted to assess the predictive value of OM and local inflammation on the occurrence of mid- and long-term adverse cardiovascular events.Method: Between 2008 and 2015, 86 atheromatous samples were harvested during femoral endarterectomy on 81 patients and processed for histomorphological analyses of calcifications and inflammation (monocytes and B cells). Histological findings were compared with the long-term follow-up of patients, including major adverse cardiac event (MACE), major adverse limb event (MALE), and mortality. Frequencies were presented as percentage, and continuous data, as mean and standard deviation. A P-value < 0.05 was considered statistically significant.Results: Median follow-up was 42.4 months (26.9-58.8). Twenty-eight percent of patients underwent a MACE; a MALE occurred in 18 (21%) limbs. Survival rate was 87.2% at 36 months. OM was found in 41 samples (51%), without any significant impact on the occurrence of MACE, MALE, or mortality. Preoperative white blood cell formulae revealed a higher rate of neutrophils associated with MACE (P = 0.04) and MALE (P = 0.0008), correlated with higher B cells counts in plaque samples.Conclusions: OM is part of femoral calcifications in almost 50% of the cases but does not seem to be an independent predictive variable for MACE or MALE. However, a higher rate of B cell infiltration of the plaque and preoperative neutrophil blood count may be predictive of adverse events during follow-up

Human serum and platelet lysate are appropriate xeno-free alternatives for clinical-grade production of human MuStem cell batches

Abstract Background Canine MuStem cells have demonstrated regenerative efficacy in a dog model of muscular dystrophy, and the recent characterization of human counterparts (hMuStem) has highlighted the therapeutic potential of this muscle-derived stem cell population. To date, these cells have only been generated in research-grade conditions. However, evaluation of the clinical efficacy of any such therapy will require the production of hMuStem cells in compliance with good manufacturing practices (GMPs). Because the current use of fetal bovine serum (FBS) to isolate and expand hMuStem cells raises several ethical, safety, and supply concerns, we assessed the use of two alternative xeno-free blood derivatives: human serum (HS) and a human platelet lysate (hPL). Methods hMuStem cells were isolated and expanded in vitro in either HS-supplemented or hPL-supplemented media and the proliferation rate, clonogenicity, myogenic commitment potential, and oligopotency compared with that observed in FBS-supplemented medium. Flow cytometry and high-throughput 3′-digital gene expression RNA sequencing were used to characterize the phenotype and global gene expression pattern of hMuStem cells cultured with HS or hPL. Results HS-supplemented and hPL-supplemented media both supported the isolation and long-term proliferation of hMuStem cells. Compared with FBS-based medium, both supplements enhanced clonogenicity and allowed for a reduction in growth factor supplementation. Neither supplement altered the cell lineage pattern of hMuStem cells. In vitro differentiation assays revealed a decrease in myogenic commitment and in the fusion ability of hMuStem cells when cultured with hPL. In return, this reduction of myogenic potential in hPL-supplemented cultures was rapidly reversed by substitution of hPL with HS or fibrinogen-depleted hPL. Moreover, culture of hMuStem cells in hPL hydrogel and fibrinogen-depleted hPL demonstrated that myogenic differentiation potential is maintained in heparin-free hPL derivatives. Conclusions Our findings indicate that HS and hPL are efficient and viable alternatives to FBS for the preparation of hMuStem cell batches in compliance with GMPs

Human MuStem cells, a promising therapeutic candidate for muscular dystrophies with immunomodulatory properties

Nowadays, allogeneic cell-based therapeutic approaches for regenerative medecine are limited by graft rejection. To counteract this major deleterious effect, immunosuppressive regimens are developed and given to patients, improving their lifespan but causing in return severe adverse effects. Over the last years, a number of adult stem cell populations including mesenchymal stem cells (MSC) and vessel-associated stem cells were described for the treatment of genetic muscle diseases. Those cells were shown to display immunomodulatory properties by acting, directly or through the secretion of soluble factors, on a large number of immune cell partners (Cossu et al., 2012; English et al., 2013). Duchenne Muscular Dystrophy (DMD) is a degenerative muscle disease characterized notably by an inflammatory component that negatively impacts on muscle regeneration activity. In this context, these original immune features attributed to stem cells could be a great advantage to improve cell engraftment and efficiency. In the laboratory, we have isolated a population of muscle-derived stem cells from healthy dog muscle tissue, called cMuStem cells, and made the proof of concept of their systemic delivery efficiency in the preclinical GRMD canine model of DMD (Rouger et al, 2011; Robriquet et al, 2015). Recently, we managed to isolate the same population from Paravertebralis muscle of 9 to 15-years old patients free of known muscle disease (hMuStem cells). It was defined as a mixed population composed of both myogenic progenitors and mesenchymal perivascular cells, and characterized by a large proliferation rate, an oligopotency as well as an in vivo myogenic regenerative potential. The aim of the study was to determine whether hMuStem cells also exhibit immunomodulatory properties. Interestingly, our preliminary data show the ability of hMuStem cells from different donors to modulate allogeneic T cell proliferation and to secrete various immunomodulatory molecules (prostaglandin-E2, indoleamin-2,3-deoxygenase-1, heme oxygenase-1 and inducible nitric-oxide synthase-1). Our data also suggest that hMuStem cells are able to interact with the complement system by inhibiting complement-mediated lysis of erythrocytes. This effect seems to be mediated by factor H, an alternative inhibitory complement pathway. Overall, our study is critical for the understanding of the interaction between MuStem cells and the immune system, as well as the design of safe and efficient allogeneic stem cell-based therapy for the treatment of muscular dystrophies

Immunomodulatory properties of human MuStem cells: assessing their impact on adaptive and innate immunity

Several preclinical approaches based on allogeneic stem cell delivery were shown to be attractive for the treatment of genetic muscular dystrophies. Nevertheless, a significant hurdle for their clinical translation is the immune rejection of donor cells. Immunosuppressive regimens are generally used to overcome host immunity and can allow the improvement of graft survival. Nevertheless, they are associated with a number of side effects, limiting their long term use. Recently, some tissue-specific adult stem cell populations were described to exhibit immunomodulatory properties that could increase their ability to engraft in an allogeneic recipient and improve their regenerative potential. We have previously demonstrated that allogeneic muscle-derived delayed adherent stem cells (that we called MuStem cells) are able to phenotypically and clin- ically correct the Duchenne dystrophic canine model (Rouger et al., 2011; Robriquet et al., 2015). Recently, we isolated human MuStem cells and assessed their immunomodulatory potential. We evaluated their ability to inhibit T cell prolif- eration and to modulate the complement pathway. Interest- ingly, our preliminary data showed that human MuStem cells were able to modulate allogeneic T cell proliferation and to express immunomodulatory molecules such as prostaglandin- E2, indoleamin-2,3-deoxygenase-1 and TGFb2. Moreover, MuStem cells were also able to secrete Factor H molecule suggesting a potential effect on the alternate pathway of the complement system. Overall, our study is critical for the un- derstanding of the crosstalk between MuStem cells and the im- mune system, as well as the design of safe and efficient allogeneic stem cell-based therapy for the treatment of muscle dystrophie

Implication of molecular vascular smooth muscle cell heterogeneity among arterial beds in arterial calcification

International audienceVascular calcification is a strong and independent predictive factor for cardiovascular complications and mortality. Our previous work identified important discrepancies in plaque composition and calcification types between carotid and femoral arteries. The objective of this study is to further characterize and understand the heterogeneity in vascular calcifica-tion among vascular beds, and to identify molecular mechanisms underlying this process. We established ECLAGEN biocollection that encompasses human atherosclerotic lesions and healthy arteries from different locations (abdominal, thoracic aorta, carotid, femoral, and infrapopliteal arteries) for histological, cell isolation, and transcriptomic analysis. Our results show that lesion composition differs between these locations. Femoral arteries are the most calcified arteries overall. They develop denser calcifications (sheet-like, nodule), and are highly susceptible to osteoid metaplasia. These discrepancies may derive from intrinsic differences between SMCs originating from these locations, as microarray analysis showed specific transcriptomic profiles between primary SMCs isolated from each arterial bed. These molecular differences translated into functional disparities. SMC from femoral arteries showed the highest propensity to mineralize due to an increase in basal TGFβ sig-naling. Our results suggest that biological heterogeneity of resident vascular cells between arterial beds, reflected by our transcriptomic analysis, is critical in understanding plaque biology and calcification, and may have strong implications in vascular therapeutic approaches

Demonstration of immunomodulatory properties for human MuStem cell population, a promising candidate for cell therapy of muscular dystrophies

International audienc

Demonstration of immunomodulatory properties for the human MuStem cell population, a promising candidate for cell therapy of muscular dystrophies

Demonstration of immunomodulatory properties for the human MuStem cell population, a promising candidate for cell therapy of muscular dystrophies. 2nd annual meeting of French Society for Stem Cell Researc

Additional file 6: of Human serum and platelet lysate are appropriate xeno-free alternatives for clinical-grade production of human MuStem cell batches

Figure S1. Influence of heparin on hMuStem cell proliferation rates. hMuStem cellsHS cultured for 6 days in HS-GM without heparin or with increasing doses of heparin (0.5–5 IU/ml). Population doublings (PDs) determined in three independent cell batches (ap < 0.05, bp < 0.01 versus HS-GM without heparin; LME model followed by Tukey’s post-hoc test) (PDF 34 kb