Bone marrow-derived progenitor cells attenuate inflammation in lipopolysaccharide-induced acute respiratory distress syndrome

Neysan Rafat,Gregor Kowanetz,Grietje Beck,Christine Dacho,Christian Betzen,Benito Yard,Burkhard Tönshoff

doi:10.1186/1756-0500-7-613

Abstract

BackgroundAcute respiratory distress syndrome (ARDS) is the most common cause of respiratory failure among critically ill patients. Novel treatment strategies are required to address this common clinical problem. The application of exogenous adult stem cells was associated with a beneficial outcome in various pre-clinical models of ARDS. In the present study we evaluated the functional capacity and homing ability of bone marrow-derived progenitor cells (BMDPC) in vitro and investigated their potential as a treatment strategy in lipopolysaccharide (LPS)-induced ARDS.ResultsEvaluation of the BMDPC showed functional capacity to form endothelial outgrowth cell colonies, which stained positive for CD133 and CD31. Furthermore, DiI-stained BMDPC were demonstrated to home to injured lung tissue. Rats treated with BMDPC showed significantly reduced histopathological changes, a reduced expression of ICAM-1 and VCAM-1 by the lung tissue, an inhibition of proinflammatory cytokine synthesis, a reduced weight loss and a reduced mortality (p < 0.03) compared to rats treated with LPS alone.ConclusionsThese findings suggest that the application of exogenous BMDPC can attenuate inflammation in LPS-induced ARDS and thereby reduce the severity of septic organ damage. Cell therapy strategies using adult stem cells might therefore become a novel and alternative option in ARDS therapy.

Highlights

Acute respiratory distress syndrome (ARDS) is the most common cause of respiratory failure among critically ill patients
We have previously demonstrated that the application of bone marrow-derived progenitor cells (BMDPC) in an endotoxin-induced ARDS rat model lead to an improved gas exchange, an inhibition of proinflammatory cytokine synthesis, an improved clinical course and a reduced mortality [15]
We have not looked at the functional capacity of the administered BMDPC to prove that they are responsible for the improved clinical course and reduced mortality

Summary

Introduction

Acute respiratory distress syndrome (ARDS) is the most common cause of respiratory failure among critically ill patients. In the present study we evaluated the functional capacity and homing ability of bone marrow-derived progenitor cells (BMDPC) in vitro and investigated their potential as a treatment strategy in lipopolysaccharide (LPS)-induced ARDS. A vast amount of pre-clinical studies have been conducted to investigate the potential of mobilization or administration of BMDPC in lung regeneration in different lung disorders [13] It is still unclear whether progenitor cells can beneficially influence regeneration of ARDS and which cell population should be used. In the present study, we investigated in our isolated endotoxin-induced ARDS rat model on one hand whether exogenically administered bone marrow-derived CD133+ progenitor cells could beneficially improve inflammation and survival. We evaluated the functional capacity and homing ability of the BMDPC, which were applied in our model

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Results

Discussion

Conclusion