isolation-splenic-microvesicles-murine-model-intraperitoneal

Isolation of Splenic Microvesicles in a Murine Model of Intraperitoneal Bacterial Infection

Microvesicles (MVs) are submicron fragments released from the plasma membrane of activated cells that act as proinflammatory and procoagulant cellular ...

new-islet-model-for-3d-study-endothelial-cell-interactions-relevance

New Islet Model for 3D Study of Endothelial and &#946; Cell Interactions: Relevance for the Screening of Cytoprotective Agents

This protocol details an optimized method for the production of small stable spheroids, their culture, and 3D imaging, for the study of the endothelial ...

Universite de Strasbourg

INSERM (French National Institute of Health and Medical Research)

University of Strasbourg

Markers of early pancreatic islet graft dysfunction and its causes are lacking. We monitored 19 type 1 diabetes islet-transplanted patients for up to 36 months following last islet injection. Patients were categorized as Partial (PS) or complete (S) Success, or Graft Failure (F), using the β-score as an indicator of graft function. F was the subset reference of maximum worsened graft outcome. To identify the immune, pancreatic, and liver contribution to the graft dysfunction, the cell origin and concentration of circulating microvesicles (MVs) were assessed, including MVs from insulin-secreting β-cells typified by polysialic acid of neural cell adhesion molecule (PSA-NCAM), and data were compared with values of the β-score. Similar ranges of PSA-NCAM -MVs were found in healthy volunteers and S patients, indicating minimal cell damage. In PS, a 2-fold elevation in PSA-NCAM -MVs preceded each β-score drop along with a concomitant rise in insulin needs, suggesting β-cell damage or altered function. Significant elevation of liver asialoglycoprotein receptor (ASGPR) -MVs, endothelial CD105 -MVs, neutrophil CD66b -MVs, monocyte CD 14 -MVs, and T4 lymphocyte CD4 -MVs occurred before each β-score drop, CD8 -MVs increased only in F, and B lymphocyte CD19 -MVs remained undetectable. In conclusion, PSA-NCAM -MVs are noninvasive early markers of transplant dysfunction, while ASGPR -MVs signal host tissue remodeling. Leukocyte MVs could identify the cause of graft dysfunction.

Assessment of plasma microvesicles to monitor pancreatic islet graft dysfunction: Beta cell- and leukocyte-derived microvesicles as specific features in a pilot longitudinal study.

Long term survival post lung transplantation (LTx) is limited by the occurrence of bronchiolitis obliterans syndrome (BOS). One mechanism involved is the epithelial-mesenchymal transition (EMT). Membrane microparticles (MPs) are known to be involved in some respiratory diseases and in other organs allograft rejection episodes. We hypothesized that leukocyte-derived MPs likely contribute to EMT. To emphasize this physiological concept, our objectives were to: (1) confirm the presence of EMT on explanted lungs from patients who underwent a second LTx for BOS; 2) characterize circulating MPs in transplanted patients, with or without BOS; (3) evaluate in vitro the effect of monocyte-derived MPs in EMT of human bronchial epithelial cells. Our IHC analysis on explanted graft lungs revealed significant pathological signs of EMT with an inhomogeneous destruction of the bronchial epithelium, with decreased expression of the epithelial protein E-cadherin and increased expression of the mesenchymal protein Vimentin. The immunophenotyping of MPs demonstrated that the concentration of MPs carrying E-cadherin was lower in patients affected by BOS (p = .007). In vitro, monocyte-derived MPs produced with LPS were associated with decreased E-cadherin expression (p < .05) along with significant morphological and functional cell modifications. MPs may play a role in EMT onset in bronchial epithelium following LTx.

Epithelial-mesenchymal transition and membrane microparticles: Potential implications for bronchiolitis obliterans syndrome after lung transplantation.

Mesenchymal stem cells (MSCs) participate in the dynamic remodeling of the extracellular matrix during wound healing, natural bleeding processes or cancer progression. Pericellular proteolysis is a key mechanism mediating the aforementioned processes.

Tranexamic acid impairs plasmin generation on human mesenchymal stem cells and derived membrane microvesicles, halting pericellular proteolysis.

Ectonucleotidases regulate extracellular purine signaling and play a key role in inflammation and thrombosis, two major components of COVID-19 pathophysiology. We investigated the enzymatic activities of CD39 (NTPDase1) and CD73 (ecto-5’-nucleotidase) as potential biomarkers of disease severity. Patients with RT-PCR-confirmed COVID-19 were enrolled between August 1st, 2020, and August 1st, 2021, and stratified into mild to moderate (MM,  = 55) or severe to critical (SC,  = 30) groups according to WHO criteria. Serum samples were collected on days 1, 3, and 7 following Emergency Department (ED) admission. CD39 and CD73 activities were measured by HPLC using etheno-fluorescent nucleotide substrates and compared to healthy volunteers (HV,  = 30) matched for age and sex. Serum CD73 activity was significantly elevated in COVID-19 patients compared to HV (MM: 76 ± 9.4; SC: 99 ± 21 vs. HV: 25 ± 2.7 pmol/min/µL;  < 0.0001), particularly in patients requiring ≥ 6 L/min oxygen ( = 0.005) or with a respiratory rate > 20/min ( = 0.02). CD73 activity remained elevated throughout hospitalization. Conversely, febrile patients (≥ 38 °C) and those with CRP ≥ 100 mg/L exhibited significantly lower CD73 activity ( = 0.023 and  = 0.004, respectively). CD39 activity was undetectable in 28.2% of patients and showed no association with disease severity or outcome. The lowest CD73 levels were observed in patients requiring oxygen therapy for ≥ 30 days and in those who died before day 7. Serum CD73 activity is associated with hypoxemia and oxygen requirements upon ED admission. Conversely, low CD73 activity reflects a hyperinflammatory state and worse outcomes, supporting its potential use in biomarker-based risk stratification for COVID-19.

ArticleTotal : 2	Year
Publication title Cited by 4	2022
Publication title	2026

Article	Year
Assessment of plasma microvesicles to monitor pancreatic islet graft dysfunction: Beta cell- and leukocyte-derived microvesicles as specific features in a pilot longitudinal study. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons\| PubMed ID: 31319009	2020
Epithelial-mesenchymal transition and membrane microparticles: Potential implications for bronchiolitis obliterans syndrome after lung transplantation. Transplant immunology\| PubMed ID: 32097721	2020
Tranexamic acid impairs plasmin generation on human mesenchymal stem cells and derived membrane microvesicles, halting pericellular proteolysis. Frontiers in medicine\| PubMed ID: 40662070	2025
Serum CD73 activity as a biomarker of hypoxemia in COVID-19 patients. Scientific reports\| PubMed ID: 41748828	2026

Fatiha El Ghazouani

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