Abstract 199: Administration of Mesenchymal Stem Cells Overexpressing Angiopoietin-1 Rescues Acute Lung Injury Induced by Lipopolysaccharide
Acute lung injury (ALI) results in increased pulmonary vascular permeability and inflammation, contributing significantly to morbidity in ICU patients. We examined the effects of mesenchymal stem cells (MSCs), with or without transfection with Angiopoietin-1 (Ang1), on the lung microvasculature in mice with ALI.
Methods: MSCs (Tulane University) were transfected (Amaxa) with human Ang1 (pAng1). Ang1 protein was detected by ELISA after 24h (724±283 pg/mL supernatant) and expression was sustained (≤ 5 days). MSCs (2.5x105) were injected into the jugular vein of C57Bl/6J mice 30 min after intratracheal instillation of 0.8mg lipopolysaccharide (LPS) to induce lung injury (n=5 / group).
Results: There was a 19-fold increase in total inflammatory cells in bronchoalveolar lavage (BAL) collected 3 days after LPS, which was reduced by 53% in MSCs-treated mice (non-/null-transfected), and by 96% with Ang1-transfected MSCs (MSCs-pAng1)(Fig⇓). Total protein and plasma albumin in BAL, both indicators of vascular leakiness in the lung, showed significant decreases in mice treated with MSCs-pAng1 compared to untreated injured mice (p<0.05). Levels of inflammatory cytokines INFγ and TNFα in BAL were also significantly reduced by MSCs-pAng1 (p<0.05). Blinded quantification of interalveolar septal thickness indicated a reduction for MSCs-treated mice (p<0.05) versus untreated injured mice.
Conclusions: Treatment with MSCs alone reduced permeability and vascular inflammation following lung injury, while Ang1 overexpression produced a near complete rescue of ALI in this model. These results support the potential benefits of cell-based Ang1 gene therapy to treat ALI.