ESICM LIVES 2019 : Berlin, Germany. 28 September - 2 October 2019

INTRODUCTION. Models of gram negative bacteria induced acute respiratory distress syndrome (ARDS) have been well established in rats. The therapeutic role of mesenchymal stromal/stem cells (MSCs) looks promising in such a model (1). Contrarily, no information is available on the role of MSCs in the treatment of pulmonary ARDS induced by gram positive bacteria. Staphylococcus Aureus is a clinically relevant gram positive bacteria, which is associated with >40% health care pneumonia cases and with mortality rates of >50% (2). OBJECTIVES. Objectives of our investigation were: 1. to establish a model of gram positive bacterial pneumonia using a clinically relevant strain of S. Aureus from a human isolate (Newman) (3); 2. To evaluate the potential therapeutic role of naïve and preactivated umbilical cord (UC) MSCs freshly harvested from culture in the treatment of acute lung injury in a new model of Rodent S. Aureus–induced ARDS. METHODS. Adult male Sprague Dawley rats underwent intratracheal instillation of S. Aureus Newman to induce pulmonary ARDS. Animals were randomized, within 2 hours post infection, to intravenous administration of: (1) vehicle (phosphate buffered saline (PBS)); (2) 1x10^7/kg fresh UC-MSCs; and (3) 1x10^7/kg fresh UCMSCs preactivated for 24 hours with cytomix (TNF-α; IL-1β; and IFN- γ [50 ng/mL each]). Comparisons among the groups were tested for differences in bacterial load and white blood cell count in the bronchoalveolar lavage (BAL), and arterial oxygenation after 48 hours. RESULTS. Endotracheal instillation of S. Aureus Newman induced a model of moderate ARDS in rats. Fresh naïve UC-MSCs did not treat the lung injury at 48 hour post infection. In contrast, the preactivation of fresh UC-MSCs with cytomix for 24 hours allowed to significantly increase the pulmonary bacterial clearance – as shown by the lower bacterial load in the BAL (Figure 1A), to reduce the lung cell infiltrates – as shown by the lower white blood cell count in the BAL (Figure 1B), and to improve oxygenation with an average PaO2/FiO2 ratio above 300 at an FiO2 of 1.0 (data not shown). Data are expressed as mean (SEM). n=6-8 per group. p-UC-MSCs=preactivated UC-MSCs. CONCLUSION. Fresh preactivated UC-MSCs therapy decreased the severity of S. Aureus induced ARDS by the reduction of bacterial load and white blood cell infiltrates into the lungs, and by the increase of arterial oxygenation. The use of preactivated UC-MSCs could represent a potential clinically relevant treatment of acute lung injury in patients with gram positive induced ARDS.