Distinct hematopoietic support by two human stromal cell lines

International audienceObjective. The hematopoietic microenvironment is complex, and the role of myofibroblast in its function is crucial. In order to obtain a stable model reflecting this particular cell type, we have previously established human bone marrow cell lines from primary myofibroblastic Stro1 ϩ population (pStro1 ϩ). We placed HPV16 E6 and E7 expression under the control of different promoters. Here, we have characterized and studied the hematopoietic support for two cell lines corresponding to the promoters ␣-SM (␣ SM-56 line) and SV40 (SV40-56 line). Materials and Methods. The expression profile was analyzed at the RNA level by gene array and at the protein level by Western blot, flow cytometry, and ELISA. Hematopoietic support determined using colony-forming unit (CFU) and stroma-adherent colony-forming cell (SA-CFC) assays. Results. The phenotype of cell lines was not significantly modified compared with primary myofibroblastic cells. They secreted a broad spectrum of hematopoietic cytokines and nonspecific mediators. The two lines allowed the growth of hematopoietic precursors and had different support capabilities. Conclusions. We have extensively characterized two novel human bone marrow stromal cell lines. They retained a myofibroblastic phenotype and have substantial but different hematopoietic support capabilities. These lines provided a basis for determining stromal factors involved in stem-cell regulation

Evaluation de la qualité des plantes potagères : guide d’échantillonnage et bases de données

National audienceDans le contexte de l’évaluation des risques environnementaux et sanitaires, un guide d’échantillonnage des plantes potagères et une base de données des concentrations en polluants inorganiques ont été élaborés et réactualisés. A l’initiative de l’ADEME et de l’INERIS, ce travail est le fruit d’une réflexion concertée entre des universitaires, des structures institutionnelles et des bureaux d’étude. Les principales étapes ont été : - une recherche bibliographique pour collecter les publications relatives aux concentrations en polluants métalliques dans les plantes potagères ; - une enquête auprès des bureaux d’études pour recueillir leurs avis sur les outils disponibles (retour d’expérience sur leur connaissance et/ou utilisation des outils et améliorations à y apporter); - une étude de faisabilité d’une base de données interactive sur les polluants organiques, sur le modèle de celle des polluants métalliques

Lead contamination in French children's homes and environment.

International audienceLead in homes is a well-known source of childhood lead exposure, which is still of concern due to the health effects of low lead doses. This study aims to describe lead contamination in the homes of children aged 6 months to 6 years in France (without overseas). Between October 2008 and August 2009, 484 housing units were investigated. Lead in tap water and total and leachable lead levels from floor dust, outdoor soils and paint chips were measured. X-ray fluorescence measurements were carried out on non-metallic and metallic substrates. Nationwide results are provided. The indoor floor dust lead (PbD) geometric mean (GM) was 8.8 μg/m² (0.8 μg/ft²) and 6.8 μg/m² (0.6 μg/ft²) for total and leachable lead respectively; 0.21% of homes had an indoor PbD loading above 430.5 μg/m² (40 μg/ft²). The outdoor play area concentration GM was 33.5 mg/kg and 21.7 mg/kg in total and leachable lead respectively; 1.4% of concentrations were higher than or equal to 400 mg/kg. Outdoor floor PbD GM was 44.4 μg/m² (4.1 μg/ft²) that was approximately 3.2 times higher than the GM of indoor PbD. Lead-based paint (LBP) was present in 25% of dwellings, LBP on only non-metallic substrates was present in 19% of homes and on metallic substrates in 10% of dwellings. The GM of lead concentrations in tap water was below 1 μg/L; 58% of concentrations were lower than 1 μg/L and 2.9% were higher than or equal to 10 μg/L. The age cut-off for homes with lead would be 1974 for paint and 1993 for indoor floor dust. This study provides, for the first time, a look at the state of lead contamination to which children are exposed in French housing. Moreover, it provides policy makers an estimate of the number of French dwellings sheltering children where abatement should be conducted

New onset of myasthenia gravis after treatment of systemic sclerosis by autologous hematopoietic stem cell transplantation : sustained autoimmunity or inadequate reset of tolerance?

Autologous hematopoietic stem-cell transplantation (HSCT) showed promising results for the treatment of primary severe autoimmune diseases (ADs). In this context, development of secondary AD after HSCT has exceptionally been observed, further questioning the roles of patient propensity for AD and of the HSCT procedure. Herein, we report new onset of myasthenia gravis 3 years after successful HSCT in a patient with severe systemic sclerosis, while in complete remission from her first AD. The de novo occurrence of secondary AD (myasthenia gravis) after HSCT was accompanied by the appearance of clonal T-cell expansions measured by the "immunoscope" technique in the context of an ongoing T-cell immune reconstitution. Secondary ADs are increasingly recognized after HSCT for AD. In our case, development of myasthenia followed clonal T-cell expansion. Detailed T-cell repertoire analysis may shed light on autoreactivity mechanisms after HSCT and may help to identify patients at risk

Thymic function recovery after unrelated donor cord blood or T-cell depleted HLA-haploidentical stem cell transplantation correlates with leukemia relapse

Use of alternative donors/sources of hematopoietic stem cells (HSC), such as cord blood (CB) or HLA-haploidentical (Haplo)-related donors, is associated with a significant delay in immune reconstitution after transplantation. Long-term T-cell immune reconstitution largely relies on the generation of new T cells in the recipient thymus, which can be evaluated through signal joint (sj) and beta T-cell-Receptor Excision Circles (TREC) quantification. We studied two groups of 33 and 24 children receiving, respectively, HSC Transplantation (HSCT) from an HLA-haploidentical family donor or an unrelated CB donor, for both malignant (46) and non-malignant disorders (11). Relative and absolute sj and beta-TREC values indicated comparable thymic function reconstitution at 3 and 6 months after the allograft in both groups. Compared to children with non-malignant disorders, those with hematological malignancies had significantly lower pre-transplantation TREC counts. Patients who relapsed after HSCT had a significantly less efficient thymic function both before and 6 months after HSCT with especially low beta-TREC values, this finding suggesting an impact of early intra-thymic T-cell differentiation on the occurrence of leukemia relapse

Studying genetic antagonisms as drivers of genome evolution

International audienc

Long-term immune reconstitution and T cell repertoire analysis after autologous hematopoietic stem cell transplantation in systemic sclerosis patients

International audienceThe determinants of clinical responses after autologous hematopoietic stem cell transplantation (aHSCT) in systemic sclerosis (SSc) are still unraveled. We analyzed long-term immune reconstitution (IR) and T cell receptor (TCR) repertoire diversity in 10 SSc patients, with at least 6 years simultaneous clinical and immunological follow-up after aHSCT. Patients were retrospectively classified as long-term responders (A, n = 5) or non-responders (B, n = 5), using modified Rodnan's skin score (mRSS) and forced vital capacity (FVC%). All patients had similar severe SSc before aHSCT. Number of reinjected CD34 + cells was higher in group B versus A (P = 0.02). Long-term mRSS fall >25% was more pronounced in group A (P = 0.004), the only to improve long-term FVC% >10% (P = 0.026). There was an overall trend toward increased of T cell reconstitution in group B versus A. B cells had a positive linear regression slope in group A (LRS = 11.1) and negative in group B (LRS = −11.6). TCR repertoire was disturbed before aHSCT and the percentage of polyclonal families significantly increased at long-term (P = 0.046), with no difference between groups. Despite improved skin score after aHSCT in all SSc patients, pretransplant B cell clonal expansion and faster post-transplant T cell IR in long-term non-responder/relapsing patients call for new therapeutic protocols guided by IR analysis to improve their outcome

Exposition au plomb des enfants dans leur logement. Projet Plomb-Habitat (2008-2014) : principaux résultats, retombées et perspectives

National audienceLes niveaux d’exposition au plomb ont beaucoup baissé mais demeurent une préoccupation de santé publique du fait d’une grande prévalence de l’exposition et d’effets à faibles doses, sans seuil connu. Le projet « Plomb-Habitat » a pour objectif de décrire les sources de plomb dans l’habitat, leur association avec la plombémie, et de tester des techniques de mesure et repérage des sources. Il repose sur un sous-échantillon de l’enquête de prévalence du saturnisme infantile « Saturn’Inf ». Pour la première fois en France, des mesurages environnementaux menés au sein de 484 foyers, représentatifs des 3,6 millions de logements abritant au moins un enfant âgé de six mois à six ans, ont permis de décrire la contamination en plomb dans l’eau du robinet, les poussières déposées au sol, les peintures, les aires de jeux extérieures, les parties communes et les plats et cosmétiques traditionnels. Le projet Plomb-Habitat a également permis d’identifier les déterminants environnementaux des plombémies, d’étudier dans quelle mesure la détermination des ratios isotopiques du plomb dans les compartiments environnementaux et le sang permet d’identifier les sources d’exposition, et de comparer les informations apportées par les analyses des fractions totales et acido-solubles. L’élaboration d’un modèle de prédiction des plombémies a conduit à l’évaluation de valeurs limites en plomb dans l’eau de boisson, les poussières déposées et le sol extérieur. Le corpus de données et de résultats ainsi constitué dans le cadre de Plomb-Habitat est aujourd’hui utilisable pour fonder les décisions publiques en vue de la poursuite des efforts de réduction des expositions au plomb