IL-1β primed mesenchymal stromal cells moderate hemorrhagic shock-induced vascular permeability

Background: Hemorrhagic shock (HS) corresponds to absolute hypovolemia creating an imbalance between oxygen supply and consumption. This causes an impaired hemostasis, a systemic inflammatory response, and microvascular permeability which can lead to multiple organ failure (MOF). There is no specific treatment for the endothelial dysfunction that plays a major role in the evolution towards MOF. Mesenchymal Stromal Cells (MSC) have been used in clinical trials for their immunomodulation and tissue repair capabilities for many years. Moreover, we previously showed that IL-1β-primed-MSC (MSCp) attenuated HS-induced organ injuries. The objective was to determine whether MSCp could prevent the onset of MOF after HS by preventing endothelial dysfunction. Methods: We developed a rat model: 90min of HS at a fixed Mean Arterial Pressure of 35mmHg, followed by resuscitation and transfusion. MSCp treatment was administered intravenously at the beginning of the resuscitation. After 6h, plasmatic endothelial markers, vascular permeability (Evans Blue (EB) administration) and renal and hepatic water contents (difference between wet and dry weight), were evaluated. We also evaluated the ability of MSCp to limit the adhesion of leukocytes to an activated endothelium in vitro. Results: Our results indicate that early administration of MSCp could reduce hepatic vascular leakage associated with a trend to decrease of Syndecan-1, ICAM-1, vWF and VCAM-1. In vitro, these cells are able to decrease leukocyte-endothelial cell bonding. Therefore, we suggest that MSCp are able to prevent endothelial dysfonction that contributes to liver injury.