Young Ju Jung1, Yun Young Park1, Jin Won Huh1, Sang-Bum Hong1. 1. Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; Asan Life Institute, Seoul, Korea.
Abstract
BACKGROUND: Acute respiratory distress syndrome (ARDS) is a type of acute respiratory failure in critically ill patients. Recently, several treatment modalities have been proposed for ARDS, but it still has a high mortality rate. In general, the role of mesenchymal stem cells (MSCs) in controlling inflammatory responses has been studied in various immune-associated diseases in humans and animals. However, only a few studies reported adipose-derived stem cells (ASCs), which are easier to isolate, are currently emerging as an attractive treatment option in ARDS. Therefore, in this study, we investigated the therapeutic effects of human ASCs and the regulation of inflammatory responses in an ARDS mouse model. METHODS: In the ARDS model, lipopolysaccharide (LPS) (5 mg/kg) was administered via the intra tracheal injection method. The mice were divided into the following four groups: (I) saline + medium; (II) saline + ASCs (2×105); (III) LPS + medium; (IV) LPS + ASCs. The ARDS observation time was divided into short and long term. LPS administration increased the concentration of proinflammatory cytokines, which was a consistent systemic inflammatory response. RESULTS: LPS/ASC group showed less neutrophil infiltration and less alveolar hemorrhage or congestion than did the LPS group. The lung injury scores of the LPS/ASC group were lower than those of the LPS group (3.8±0.9 vs. 6.8±1.1; P=0.03) at day 2. Compared to the LPS group, LPS/ASC group showed reduced collagen deposition around the vessels and fibrosis accompanied by alveolar septal or interstitial thickening and lower MPO levels than did the LPS group (453.2±26.2 vs. 670.2±65.9 pg/mL; P<0.01) at day 7. CONCLUSIONS: ASC therapy can inhibit neutrophil recruitment, which shows trend of reducing short term lung injury (day 2) and affecting fibrosis in long term (day 7). Further studies are warranted to understand the mechanism and improve the therapeutic effect of ASCs. 2019 Annals of Translational Medicine. All rights reserved.
BACKGROUND: Acute respiratory distress syndrome (ARDS) is a type of acute respiratory failure in critically ill patients. Recently, several treatment modalities have been proposed for ARDS, but it still has a high mortality rate. In general, the role of mesenchymal stem cells (MSCs) in controlling inflammatory responses has been studied in various immune-associated diseases in humans and animals. However, only a few studies reported adipose-derived stem cells (ASCs), which are easier to isolate, are currently emerging as an attractive treatment option in ARDS. Therefore, in this study, we investigated the therapeutic effects of human ASCs and the regulation of inflammatory responses in an ARDS mouse model. METHODS: In the ARDS model, lipopolysaccharide (LPS) (5 mg/kg) was administered via the intra tracheal injection method. The mice were divided into the following four groups: (I) saline + medium; (II) saline + ASCs (2×105); (III) LPS + medium; (IV) LPS + ASCs. The ARDS observation time was divided into short and long term. LPS administration increased the concentration of proinflammatory cytokines, which was a consistent systemic inflammatory response. RESULTS: LPS/ASC group showed less neutrophil infiltration and less alveolar hemorrhage or congestion than did the LPS group. The lung injury scores of the LPS/ASC group were lower than those of the LPS group (3.8±0.9 vs. 6.8±1.1; P=0.03) at day 2. Compared to the LPS group, LPS/ASC group showed reduced collagen deposition around the vessels and fibrosis accompanied by alveolar septal or interstitial thickening and lower MPO levels than did the LPS group (453.2±26.2 vs. 670.2±65.9 pg/mL; P<0.01) at day 7. CONCLUSIONS: ASC therapy can inhibit neutrophil recruitment, which shows trend of reducing short term lung injury (day 2) and affecting fibrosis in long term (day 7). Further studies are warranted to understand the mechanism and improve the therapeutic effect of ASCs. 2019 Annals of Translational Medicine. All rights reserved.
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