Study of immunomodulatory effects of mesenchymal stem cell-derived exosomes in a mouse model of LPS induced systemic inflammation

Life Sci. 2022 Dec 1:310:120938. doi: 10.1016/j.lfs.2022.120938. Epub 2022 Sep 20.

Abstract

Background: Sepsis is a debilitating systemic inflammation that resulted from infection or injury. Despite many advances in treatment, the resulting mortality rate has remained high due to increasing antibiotic resistance and aging communities. The present study investigated the effects of stem cell-derived exosomes in a mouse model of LPS-induced systemic inflammation.

Materials and methods: To induce sepsis, the LPS model was used. Mice were divided into three groups: normal, patient group (LPS + PBS), and treatment group (LPS + exosome). The treatment group received an intravenous exosome 1 h after induction of the model. Patient and treatment groups were sacrificed at 4, 6, 24, and 48 h after induction of the model, and their tissues were isolated. Blood samples were taken from animal hearts to perform biochemical and immunological tests. The study results were analyzed using Graph Pad Prism software version 9.

Results: Mesenchymal stem cell-derived exosomes decreased serum levels of ALT and AST liver enzymes, decreased neutrophil to lymphocyte ratio (NLR), and improved kidney, liver, and lung tissue damage at 4, 6, and 24 h after model induction. At 24 h, the exosomes were able to reduce serum urea levels. This study revealed decreased levels of inflammatory cytokines such as IL-6, IL-1β, and TNF-α after exosome injection.

Conclusion: Our findings suggest that treating mice with stem cell-derived exosomes can ameliorate the destructive effects of inflammation caused by sepsis by reducing inflammatory factors and tissue damage.

Keywords: Exosome; Extracellular vesicles; Lipopolysaccharide; Mesenchymal stem cell; Sepsis; Sepsis mouse model.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Exosomes*
  • Inflammation
  • Lipopolysaccharides / toxicity
  • Mesenchymal Stem Cells*
  • Mice
  • Mice, Inbred C57BL
  • Sepsis* / chemically induced
  • Sepsis* / therapy

Substances

  • Lipopolysaccharides