Human adult bone marrow-derived stem cells decrease severity of lipopolysaccharide-induced acute respiratory distress syndrome in sheep

Mauricio Rojas,Nayra Cárdenes,Robert Deans,Ergin Kocyildirim,Eder Cáceres,John R Tedrow,Christian Bermúdez,Anthony Ting

doi:10.1186/scrt430

Abstract

IntroductionAcute respiratory distress syndrome (ARDS) is the most common cause of respiratory failure among critically ill subjects, sepsis and severe bacterial pneumonia being its most common causes. The only interventions that have proven beneficial are protective ventilation strategies and fluid conservation approaches. New therapies are needed to address this common clinical problem. Others and we have previously shown the beneficial effect of infusion of exogenous adult stem cells in different pre-clinical models of ARDS.MethodsIn the present study endotoxin was infused intravenously into 14 sheep from which 6 received different doses of adult stem cells by intrabronchial delivery to evaluate the effect of stem cell therapy.ResultsAfter administration of endotoxin, there was a rapid decline in oxygenation to hypoxemic values, indicative of severe-to-moderate ARDS. None of the animals treated with saline solution recovered to normal baseline values during the 6 hours that the animals were followed. In contrast, sheep treated with a dose of 40 million adult stem cells returned their levels of oxygen in their blood to baseline two hours after the cells were infused. Similarly, improvements in carbon dioxide (CO2) clearance, pulmonary vascular pressures and inflammation were observed and confirmed by histology and by the decrease in lung edema.ConclusionsWe concluded that instillation of adult non-hematopoietic stem cells can diminish the impact of endotoxin and accelerate recovery of oxygenation, CO2 removal and inflammation in the ovine model, making the use of adult stem cells a real alternative for future therapies for ARDS.

Highlights

Acute respiratory distress syndrome (ARDS) is the most common cause of respiratory failure among critically ill subjects, sepsis and severe bacterial pneumonia being its most common causes
We concluded that instillation of adult non-hematopoietic stem cells can diminish the impact of endotoxin and accelerate recovery of oxygenation, CO2 removal and inflammation in the ovine model, making the use of adult stem cells a real alternative for future therapies for ARDS
We first evaluated the effect of endotoxin on changes in lung function; as we show in Figure 2A, endotoxin was administered intravenously and blood gas analysis demonstrated an induction of moderate-to-severe ARDS by the partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) levels

Summary

Introduction

Acute respiratory distress syndrome (ARDS) is the most common cause of respiratory failure among critically ill subjects, sepsis and severe bacterial pneumonia being its most common causes. Others and we have previously shown the beneficial effect of infusion of exogenous adult stem cells in different pre-clinical models of ARDS. Acute respiratory distress syndrome (ARDS) is a common clinical entity and a major cause of morbidity and mortality in the critical care setting [1]. ARDS results from a wide variety of disorders, sepsis is its main cause and the risk factor most associated with high mortality [4,5,6]. In addition to the alveolar damage, there is an influx of circulating inflammatory cells and formation of hyaline membranes usually caused by the mechanical ventilation. If the inflammatory process is severe enough, there will be ensuing disorganized repair resulting in fibrosis [13]

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Conclusion