Combined Effects of Mesenchymal Stromal Cells and Antibiotic Therapy on Enterobacter Ventilator-Associated Pneumonia in Rabbits

Mesenchymal stromal cells (MSCs) enhance outcomes and attenuate the inflammatory response in preclinical models of community-acquired pneumosepsis. Ventilator-associated pneumonia (VAP), a major cause of mortality in intensive care units, is closely linked to immune dysfunction. This study aimed to evaluate whether MSCs combined with an antibiotic (cefepime) could improve outcomes and restore immune and metabolic cellular homeostasis in a preclinical model of VAP, compared to cefepime alone. Overall design: Male rabbits underwent protective mechanical ventilation and received an injection of LPS (3 ng/kg) to mimic the effects of an initial infectious challenge and associated immune alterations. Twenty-four hours later, they were inoculated intratracheally with an Enterobacter aerogenes strain to induce VAP. Rabbits (10/group) were randomly assigned to receive either human umbilical cord-derived MSCs (3.10^6/kg, intravenous) or sodium chloride, 4 hours after the Enterobacter challenge. All animales were treated with an antibiotic (cefepime). Lung bacterial concentrations (primary outcome), systemic bacterial burden, 24-hour survival post-bacterial challenge, lung injury, immune and mitochondrial dysfunctions were evaluated.