Publications

Human endoglin as a potential new partner involved in platelet–endothelium interactions

A Highway for Disinformation? The Alarming Exodus of Scientists from Twitter/X and its Consequences

Activation endothéliale associée aux ANCA IgA au cours des lésions de lésions acrales pendant l’épidémie de COVID-19

Multidimensional Proteomic Approach of Endothelial Progenitors Demonstrate Expression of KDR Restricted to CD19 Cells

Curative anticoagulation prevents endothelial lesion in COVID‐19 patients

The profibrotic cytokine transforming growth factor‐β1 increases endothelial progenitor cell angiogenic properties

Les progéniteurs endothéliaux comme produit de thérapie cellulaire des pathologies cardiovasculaires?

L'injection de progeniteurs endotheliaux (PEC) cultives ex vivo ou provenant de cellules mononucleees medullaires a montre une efficacite dans les modeles precliniques et cliniques de neovascularisation. Cependant, l'origine et la definition exacte de la population de cellules responsable de ces benefices cliniques restent controversees. Etant donne l'utilite potentielle des PEC comme produit de therapie cellulaire, leur caracterisation moleculaire est primordiale. Nous decrivons ici les deux principaux types de PEC obtenus en culture cellulaire, et la mise en evidence par notre equipe des BMP2/4 comme marqueurs de PEC tardifs qui, de plus, jouent un role important dans la differenciation et l'expansion des PEC. Cette revue recapitule egalement les differentes methodes decrites pour l'expansion ex vivo des PEC qui, dans la plupart des cas, sont issus de sang de cordon et s'averent difficilement transposables aux PEC de sang adulte. Ainsi, une des possibilites therapeutiques serait de deriver des cellules endotheliales a partir de cellules souches embryonnaires (cellules ES) ou, mieux encore, de cellules « iPS » (induced pluripotent stem cells) produites a partir de cellules adultes autologues. Leur utilisation comme produit de therapie cellulaire des maladies cardiovasculaires pose encore actuellement des problemes ethiques, d'une part, en ce qui concerne les cellules ES, et d'effets indesirables d'autre part, comme le risque de formation de teratomes. Enfin, la meilleure comprehension des facteurs impliques dans les proprietes de pluripotence, d'autorenouvellement et de differenciation permettra de mieux maitriser la biologie des cellules souches adultes.

Fibrin monomers evaluation during hospitalization for COVID-19 is a predictive marker of in-hospital mortality

Background Coagulopathy is one of the main triggers of severity and worsening of Coronavirus disease 2019 (COVID-19) particularly in critically ill patients. D-dimer has been widely used to detect COVID-19 coagulation disorders and has been correlated with outcomes such as disease severity and in-hospital mortality. Involvement of other fibrin degradation products, particularly fibrin monomers (FM), remains an ongoing question. Methods We performed a monocentric study of adult patients with COVID-19, who were admitted either in the medical ward (MW) or in the intensive care unit (ICU) and who had FM measurements performed on them during the first wave of COVID-19 outbreak. We analyzed the positivity of FM levels (FM > 7 µg/mL) to assess the ability of FM monitoring during the first days of hospitalization to predict COVID-19 outcomes. Results In our cohort, 935 FM measurements were performed in 246 patients during their first 9 days of hospitalization. During patient follow-up, the FM levels were higher in patients admitted directly to the ICU than in those admitted to the MW. Moreover, we observed significantly increased levels of FM in patients when the data were stratified for in-hospital mortality. At hospital admission, only 27 (11%) patients displayed a positive value for FM; this subgroup did not differ from other patients in terms of severity (indicated by ICU referral at admission) or in-hospital mortality. When analyzing FM positivity in the first 9 days of hospitalization, we found that 37% of patients had positive FM at least once during hospitalization and these patients had increased in-hospital mortality ( p = 0.001). Thus, we used non-adjusted Kaplan–Meier curves for in-hospital mortality according to FM positivity during hospitalization and we observed a statistically significant difference for in-hospital mortality (hazard ratio = 1.48, 95% CI: 1.25–1.76, p < 0.001). However, we compared the AUC of FM positivity associated with a ratio of D-dimer >70% and found that this combined receiver operating characteristic (ROC) curve was superior to the FM positivity ROC curve alone. Conclusion Monitoring of FM positivity in hospitalized patients with COVID-19 could be a reliable and helpful tool to predict the worsening condition and mortality of COVID-19.

Bone-marrow-derived very small embryonic-like stem cells in patients with critical leg ischaemia: evidence of vasculogenic potential

Summary Very small embryonic-like stem cells (VSELs) are multipotent stem cells localised in adult bone marrow (BM) that may be mobilised into peripheral blood (PB) in response to tissue injury. We aimed to quantify VSELs in BM and PB of patients with critical limb ischaemia (CLI) and to test their angiogenic potential in vitro as well as their therapeutic capacity in mouse model of CLI. We isolated BM VSELs from patients with CLI and studied their potential to differentiate into vascular lineages. Flow and imaging cytometry showed that VSEL counts were lower in BM (p< 0.001) and higher (p< 0.001) in PB from CLI patients compared to healthy controls, suggesting that ischaemia may trigger VSELs mobilisation in this patient population. Sorted BM-VSELs cultured in angiogenic media acquired a mesenchymal phenotype (CD90+, Thy-1 gene positive expression). VSEL-derived cells had a pattern of secretion similar to that of endothelial progenitor cells, as they released low levels of VEGF-A and inflammatory cytokines. Noteworthy, VSELs triggered post-ischaemic revascularisation in immunodeficient mice (p< 0.05 vs PBS treatment), and acquired an endothelial phenotype either in vitro when cultured in the presence of VEGF-B (Cdh-5 gene positive expression), or in vivo in Matrigel implants (human CD31+ staining in neo-vessels from plug sections). In conclusion, VSELs are a potential new source of therapeutic cells that may give rise to cells of the endothelial lineage in humans.

Genome-wide association study of a semicontinuous trait: illustration of the impact of the modeling strategy through the study of Neutrophil Extracellular Traps levels

Abstract Over the last years, there has been a considerable expansion of genome-wide association studies (GWAS) for discovering biological pathways underlying pathological conditions or disease biomarkers. These GWAS are often limited to binary or quantitative traits analyzed through linear or logistic models, respectively. In some situations, the distribution of the outcome may require more complex modeling, such as when the outcome exhibits a semicontinuous distribution characterized by an excess of zero values followed by a non-negative and right-skewed distribution. We here investigate three different modeling for semicontinuous data: Tobit, Negative Binomial and Compound Poisson-Gamma. Using both simulated data and a real GWAS on Neutrophil Extracellular Traps (NETs), an emerging biomarker in immuno-thrombosis, we demonstrate that Compound Poisson-Gamma was the most robust model with respect to low allele frequencies and outliers. This model further identified the MIR155HG locus as significantly (P = 1.4 × 10−8) associated with NETs plasma levels in a sample of 657 participants, a locus recently highlighted to be involved in NETs formation in mice. This work highlights the importance of the modeling strategy for GWAS of a semicontinuous outcome and suggests Compound Poisson-Gamma as an elegant but neglected alternative to Negative Binomial for modeling semicontinuous outcome in the context of genomic investigations.

Hemocompatibility of Bioprosthetic valve in bovine pericardium is based on fibrin formation and its endothelization

Iconography : Neuromieliti ottiche

Treprostinil indirectly regulates endothelial colony forming cell angiogenic properties by increasing VEGF-A produced by mesenchymal stem cells

Summary Pulmonary vasodilators and prostacyclin therapy in particular, have markedly improved the outcome of patients with pulmonary hypertension (PH). Endothelial dysfunction is a key feature of PH, and we previously reported that treprostinil therapy increases number and proliferative potential of endothelial colony forming cells (ECFC) isolated from PH patients’ blood. In the present study, the objective was to determine how treprostinil contributes to the proangiogenic functions of ECFC. We examined the effect of treprostinil on ECFC obtained from cord blood in terms of colony numbers, proliferative and clonogenic properties in vitro, as well as in vivo vasculogenic properties. Surprisingly, treprostinil inhibited viability of cultured ECFC but did not modify their clonogenic properties or the endothelial differentiation potential from cord blood stem cells. Treprostinil treatment significantly increased the vessel-forming ability of ECFC combined with mesenchymal stem cells (MSC) in Matrigel implanted in nude mice. In vitro, ECFC proliferation was stimulated by conditioned media from treprostinil-pretreated MSC, and this effect was inhibited either by the use of VEGF-A blocking antibodies or siRNA VEGF-A in MSC. Silencing VEGF-A gene in MSC also blocked the pro-angiogenic effect of treprostinil in vivo. In conclusion, increased VEGF-A produced by MSC can account for the increased vessel formation observed during treprostinil treatment. The clinical relevance of these data was confirmed by the high level of VEGF-A detected in plasma from patients with paediatric PH who had been treated with treprostinil. Moreover, our results suggest that VEGF-A level in patients could be a surrogate biomarker of treprostinil efficacy.

Thrombin receptor PAR1 silencing in endothelial colony–forming cells modifies stemness and vasculogenic properties

Nitroglycerine ointment as aid to venous cannulation in children

Cooperation between human fibrocytes and endothelial progenitor cells increases angiogenesis via CXCR4 pathway

Abstract 23235: Implantation Of A Bioprosthetic Total Artificial Heart Induces A Profile Of Acquired Haemocompatibility By Recellularization Of The Blood-contacting Membrane

We report here the results of haemocompatibility in 3 patients from the feasibility study of the first-in-man trail of a novel total artificial heart (C-TAH) containing bioprosthetic blood-contacti...

A conserved transcriptional program for MAIT cells across mammalian evolution

Mucosal-associated invariant T (MAIT) cells harbor evolutionarily conserved TCRs, suggesting important functions. As human and mouse MAIT functional programs appear distinct, the evolutionarily conserved MAIT functional features remain unidentified. Using species-specific tetramers coupled to single-cell RNA sequencing, we characterized MAIT cell development in six species spanning 110 million years of evolution. Cross-species analyses revealed conserved transcriptional events underlying MAIT cell maturation, marked by ZBTB16 induction in all species. MAIT cells in human, sheep, cattle, and opossum acquired a shared type-1/17 transcriptional program, reflecting ancestral features. This program was also acquired by human iNKT cells, indicating common differentiation for innate-like T cells. Distinct type-1 and type-17 MAIT subsets developed in rodents, including pet mice and genetically diverse mouse strains. However, MAIT cells further matured in mouse intestines to acquire a remarkably conserved program characterized by concomitant expression of type-1, type-17, cytotoxicity, and tissue-repair genes. Altogether, the study provides a unifying view of the transcriptional features of innate-like T cells across evolution.