The effect of human adipose-derived stem cells on lipopolysaccharide-induced acute respiratory distress syndrome in mice

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 (2×10 5 ); (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.

Insights into the use of mesenchymal stem cells in COVID-19 mediated acute respiratory failure

“…In COVID-19-relevant animal models, administration of MSCs have resulted in amelioration of disease symptoms. In liposaccharide (LPS)-induced ARDS in mice, treatment with MSCs resulted in attenuation of neutrophil infiltration, collagen deposition and fibrosis 54 . In a similar model, administration of MSCs protected mice from LPS-induced ALI by inhibiting macrophages in a manner that was dependent on the secretion of PGE2, granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-13 51 .…”

Clinical Efficacy and Safety of Mesenchymal Stem Cells for Systemic Lupus Erythematosus

“…Cell therapy has become an attractive therapeutic strategy for various types of diseases [17][18][19][20], and it has achieved certain curative effects in induction therapy in patients with SLE [13]. The purpose of this study was to evaluate the efficacy of MSCs in the treatment of SLE by meta-analysis.…”

Therapeutic mechanisms of mesenchymal stem cells in acute respiratory distress syndrome reveal potentials for Covid-19 treatment

“…Intratracheal infusion of human AD-MSCs could significantly ameliorate lung injury by attenuated interstitial fibrosis in LPS-induced ARDS mouse models and reducing neutrophil infiltration [ 72 ]. Similarly, intravenous infusion of human UC-MSCs inhibited bleomycin-induced fibrosis in immunocompetent mice [ 70 ].…”