Abstract 19670: Adipose-derived Mesenchymal Stem Cells Attenuate Pulmonary Microvascular Hyperpermeability After Smoke Inhalation

Abstract

Pulmonary edema is a hallmark of acute respiratory distress syndrome (ARDS). Smoke inhalation causes ARDS, significantly increasing the mortality of burn patients. Mesenchymal stem cells (MSCs) exert potent anti-inflammatory properties. The goal of the present study was to test the safety and efficacy of MSCs in a well-characterized clinically relevant ovine model of ARDS. Methods: Female sheep (30-40 kg) were surgically prepared 5-7 days prior the study. ARDS was induced by cooled cotton smoke inhalation. Following the injury, sheep were ventilated, resuscitated with lactated Ringer’s solution and cardiopulmonary hemodynamics was monitored for 48 h in a conscious state. Pulmonary microvascular hyper-permeability was assessed by measuring lung lymph flow, extravascular lung water content, protein in plasma and lung lymph. Sheep were randomly allocated to two groups: 1) MSCs: infused with 5 million/kg of intravenous MSCs over 30min starting 1 h post-injury, n=5; 2) control, treated with a vehicle in a similar pattern (200ml of PlasmaLyte A), n=5. Results: Lung lymph flow, an index of pulmonary transvascular fluid flux was ~7-fold increased in control sheep compared to baseline. This was associated with a significant protein decrease in plasma and its increase in lung lymph. The treatment with MSCs significantly attenuated these changes (Table). Moreover, the treatment with MSCs almost reversed increased pulmonary vascular permeability index {(lung lymph proteinхlung lymph flow)/plasma protein} and reduced lung water content (Lung wet-to-dry weight ratio). Pulmonary gas exchange was significantly improved by MSCs (PaO2/FiO2 was 406±101 in MSCs and 262±127 in control at 24 hrs, p<0.05). Infusion of the MSCs did not affect pulmonary artery pressure and other hemodynamic variables. Conclusions: MSCs infusion was well tolerated. The results suggest that intravenous MSCs modulate pulmonary microvascular hyper-permeability and prevent onset of ARDS.