Therapeutic Effects of Bone Marrow-derived Progenitor Cells in Lipopolysaccharide-induced Acute Respiratory Distress Syndrome

Abstract

Objective: Endotoxin-induced acute respiratory distress syndrome (ARDS) is characterized by diffuse dysfunction of the microvasculature including increased permeability with oedema formation and apoptosis or necrosis of endothelial- and epithelial cells. Concomitantly, an increased concentration of circulating endothelial progenitor cells (EPC) was found in septic patients, which seem to be involved in pulmonary regeneration. The number of circulating EPC correlated inversely to disease severity and mortality. Since bone marrow-derived endothelial progenitor cells (BMDPC) were found homing to damaged lung tissue, a reparative process seems to be initiated right after the initiation of vessel damage or degeneration. In the present study we investigated the potential of BMDPC as a treatment strategy in lipopolysaccharide (LPS)-induced ARDS. Methods: Male Wistar rats received lipopolysaccharide (LPS) (25 μg/kg) systemically and directly after LPS injection, the animals were administered 1x106 suspension of CD133+-cells dissolved in 1 ml of sodium chloride 0.9% or only 1 ml sodium chloride 0.9% for the control group. Mortality, macroscopic changes in lung tissue, disease symptoms, blood gas analyses, serum cytokine concentration, wet/dry weight and long-term results were analyzed. Results: Rats treated with BMDPC showed a significantly improved pulmonary gas exchange, an inhibition of proinflammatory cytokine synthesis, an improved clinical course and a reduced mortality (p<0.024) compared to rats treated with LPS alone. Conclusions: These findings suggest that the application of exogenous BMDPC can reduce the severity of septic organ damage. Cell therapy with BMDPC might therefore become a novel option in ARDS therapy.