• Shock · Nov 2022

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

    • Xiancheng Chen, Ming Chen, Yang Yang, Can Xu, Huimin Lu, Yali Xu, Xiaojing Li, Yu Wei, Zhanghua Zhu, Yitao Ding, and Wenkui Yu.
    • Department of Critical Care Medicine, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China.
    • Shock. 2022 Nov 1; 58 (5): 417425417-425.

    AbstractBackground: 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.Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Shock Society.

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