The Study on the Regulation of Th Cells by Mesenchymal Stem Cells Through the JAK-STAT Signaling Pathway to Protect Naturally Aged Sepsis Rats

Abstract

Background: Sepsis is the leading cause of death among ICU patients, especially elderly patients. We designed this study to confirm the protective effect of MSCs against sepsis in aged rats. Methods: We used naturally aged SD rats to establish sepsis model and injected 5×106 umbilical cord-derived MSCs via the tail vein. Each group of rats was analyzed for survival, examined for biochemical parameters, stained for organ histology, and analyzed for the Th cell subpopulation ratio and inflammatory cytokine levels by flow cytometry. Western blotting was performed to detect the activity of the JAK-STAT signaling pathway. Vitro experiments were designed to confirm the effect of MSCs, and verified the possible mechanism using JAK/STAT inhibitors. Findings: The 72 h survival rate of sepsis rats treated with MSCs was significantly increased, organ damage and inflammatory infiltration were reduced, the levels of organ damage indicators were decreased, the ratios of Th1/Th2 and Th17/Treg in peripheral blood and spleen were significantly decreased, the levels of pro-inflammatory cytokines were decreased, the levels of anti-inflammatory cytokines were increased, and the levels of STAT1 and STAT3 phosphorylation were reduced. These results were validated in in vitro experiments. Interpretation: This study confirms that MSCs can control the inflammatory response induced by sepsis by regulating Th cells and inflammatory factors, and that this leads to reduction of tissue damage, protection of organ functions and ultimately improvement of survival in aged sepsis model rats. Inhibition of the JAK-STAT signaling pathway may be an important mechanism for their action. Funding Information: Not applicable. Declaration of Interests: All authors declare no competing interests. Ethics Approval Statement: This study was approved by the Ethics Committee of the Chinese PLA General Hospital. Animal experiments were approved by the Experimental Animal Welfare Ethics Committee of Chinese PLA General Hospital. Umbilical cords were obtained from the Department of Obstetrics and Gynecology, the First Medical Center, Chinese PLA General Hospital, China, and the mothers signed an informed consent.