Lipopolysaccharide-Preconditioned Mesenchymal Stem Cell Transplantation Attenuates Critical Persistent Inflammation Immune Suppression and Catabolism Syndrome in Mice

Abstract

Background: Persistent inflammation, immunosuppression, and catabolism syndrome (PIICS) is associated with high mortality and high health care costs, and there is currently no effective target treatment. Mesenchymal stem cells (MSCs) possess multipotent immunomodulatory properties. LPS-preconditioned type 1 MSCs (MSC1s) are potentially beneficial for PIICS treatment because of their proinflammatory, anti-infective, and healing properties. Here, we investigated the therapeutic efficacy and mechanisms of action of MSC1s in PIICS. Methods: We previously optimized a reaggravated PIICS mouse model, which was used in this study. PIICS mice were subjected to cecal ligation and puncture on day 1 and LPS injection on day 11. Subsequently, the mice were treated with or without MSC1s. Animal survival and phenotypes, along with the levels of catabolism, inflammation, and immunosuppression, were evaluated. MSC1s were cocultured with CD8 + T cells in vitro, and inflammatory cytokine levels and CD8 + T-cell function were assessed. Results: MSC1 transplantation alleviated weight loss and muscle wasting, inhibited catabolism and inflammation, and considerably improved the proportion and function of CD8 + T cells in the PIICS mice. After coculture with MSC1s, the expression levels of CD107a and interferon γ increased, whereas the expression level of programmed death 1 decreased significantly in CD8 + T cells. MSC1s also promoted proinflammatory cytokine secretion and reduced the concentration of soluble PD-L1 in vitro. Conclusions: MSC1s can protect mice against critical PIICS, partly by enhancing CD8 + T-cell function. Therefore, MSC1 transplantation is a novel therapeutic candidate for PIICS.

Predictive Value of Soluble Programmed Cell Death Ligand-1 in the Progression of Septic Patients to Chronic Critical Illness in the Intensive Care Unit: A Prospective Observational Clinical Study

“…In mice with persistent inflammation, immunosuppression, and catabolism, LPS-pretreated type 1 mesenchymal stem cells with proinflammatory, anti-infectious, and healing properties alleviated symptoms and improved the proportion and function of CD8 + T cells. Notably, significantly reduced levels of sPD-L1 were discovered in cocultures of type 1 mesenchymal stem cells (28). Although sPD-L1 at admission did not distinguish between the CCI and RAP groups in this study, it was a predictor of lymphocytopenia on day 7 after treatment in septic patients.…”