Effect of Preconditioned Mesenchymal Stromal Cells on Early Microvascular Disturbance in a Mouse Sepsis Model.

Abstract

Septic patients often die in a context of multiple organ dysfunction syndrome (MODS), despite the macro-hemodynamic parameters being normalized and after the onset of antibiotic therapy. Microcirculation injury during sepsis affects capillary permeability and leukocyte-endothelium interactions and is thought to be instrumental in organ injury. Several studies have demonstrated a beneficial effect of mesenchymal stromal cells (MSCs) injection on survival and organ dysfunctions in sepsis models. In vivo activity of MSCs also appears to be very much dependent on the information provided before injection. Indeed preconditioning by interferon γ (IFNγ; MSC-IFNγ) increases immunosuppressive capacity of MSCs in vitro and in vivo. Therefore, the objective was to evaluate the effect of MSC naive or IFNγ preconditioned on leukocyte-endothelium interactions in a polymicrobial sepsis model by intraperitoneal feces injection. Six hours (H6) after this induction, we used intravital microscopy in mice cremaster muscle venules to study the flow behavior of leukocytes. Plasmas were harvested to evaluate inflammation level and endothelial activation. We showed that MSC-IFNγ have a beneficial effect on microcirculation, by increasing the flow of white blood cells (WBCs) and the percentage of venules containing flowing WBCs, by significantly reducing the adhesion of WBCs and by increasing the average red blood cell velocity (VRBC). In conclusion, our results suggest that intravenous injection of preconditioned MSC-IFNγ improves microvascular hemodynamics in early phases of sepsis.

• Authors: Nathalie Baudry, Julie Starck, Clotilde Aussel, Kyle Lund, Marc Aletti, Jacques Duranteau, Sébastien Banzet, Jean-Jacques Lataillade, Eric Vicaut, Juliette Peltzer
• Journal: Stem cells and development (Stem Cells Dev) Vol. 28 Issue 24 Pg. 1595-1606 (12 15 2019) ISSN: 1557-8534 [Electronic] United States
• PMID: 31663453 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Culture Media, Conditioned
• IFNG protein, mouse
• Interferon-gamma

Topics

• Animals
• Cell Adhesion (genetics, physiology)
• Culture Media, Conditioned (pharmacology)
• Disease Models, Animal
• Endothelium (drug effects)
• Erythrocytes (drug effects)
• Humans
• Interferon-gamma (genetics)
• Leukocytes (drug effects)
• Mesenchymal Stem Cell Transplantation
• Mesenchymal Stem Cells (cytology, drug effects)
• Mice
• Microcirculation (genetics, physiology)
• Microvessels (cytology, metabolism)
• Sepsis (pathology, therapy)