Abstract
Bone marrow-derived mesenchymal stem cells (BMDMSC) are emerging as a therapeutic modality in various inflammatory disease states, including acute lung injury (ALI). A hallmark of inflammation, and a consistent observation in patients with ALI, is a perturbation in the systemic redox environment. However, little is known about the effects of BMDMSC on the systemic redox status. The objective of the present study was to determine whether exogenously infused BMDMSC protect against endotoxin-induced oxidation of plasma cysteine (Cys) and glutathione (GSH) redox states. To determine the effect on the redox state if BMDMSC, mice received endotoxin intraperitoneally (1 mg/kg), followed by intravenous infusion of either 5 × 105 BMDMSC or an equal volume of saline solution. Control mice received intraperitoneal endotoxin followed by 5 × 105 lung fibroblasts given intravenously. Cys, cystine (CySS), GSH, and glutathione disulfide (GSSG) concentrations were determined by HPLC. Results showed sequential preservation of plasma Cys and GSH levels in response to BMDMSC infusion. The data show that BMDMSC infusion leads to a more reducing Cys and GSH redox state. The findings are the first to demonstrate that BMDMSC have antioxidant effects in vivo, and add to our understanding of the systemic effects of BMDMSC in lung injury.
Highlights
The inflammatory response to pathogens, physical trauma, or toxic stimuli is critical in host defense, but excessive and unregulated inflammation can injure the lungs [1]
Enrichment of bone marrow-derived mesenchymal stem cells from crude bone marrow suspensions is achieved by selection for a plastic-adherent population that expresses neither hematopoietic nor endothelial cell surface markers but is positive for the expression of adhesion and stromal markers [3]
The main finding of the present study is that infusion of Bone marrow-derived mesenchymal stem cells (BMDMSC) is associated with an increase in systemic Cys and GSH levels, which results in the preservation of Cys and GSH redox states during endotoxemia
Summary
The inflammatory response to pathogens, physical trauma, or toxic stimuli is critical in host defense, but excessive and unregulated inflammation can injure the lungs [1]. In patients with gram negative sepsis, a disregulated inflammatory response to bacterial endotoxin increases the risk for acute lung injury (ALI), which can lead to severe respiratory failure termed the acute respiratory distress syndrome (ARDS) [1]. Several studies, including our own, have shown that exogenously infused BMDMSCs protect against endotoxininduced inflammation, and ALI in mice [4,5,6]. In these studies, the protective effects of BMDMSCs are mediated by a decrease in circulating proinflammatory cytokine levels, and appear to be independent of BMDMSCs engraftment into the lung. A hallmark of inflammation, and a consistent observation in patients with ALI, is a perturbation in
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