Human Umbilical Cord Mesenchymal Stem Cells Alleviate Concanavalin A-induced Fulminant Hepatitis by Repressing NF-κB Signaling and Glycolysis

Abstract Background: Fulminant hepatitis is a severe life-threatening clinical condition with rapid progressive loss of liver function. It is characterised by massive activation and infiltration of immune cells into the liver and disturbance of inflammatory cytokine production. Mesenchymal stem cells (MSCs) showed potent immunomodulatory properties, and transplantation of MSCs is suggested as a promising therapeutic approach for a host of inflammatory conditions. Methods: In the current study, a well-established Concanavalin A (Con A)-induced fulminant hepatitis mouse model was used to investigate the effects of transplanting human umbilical cord MSC (hUC-MSC) on fulminant hepatitis. Results: We showed that hUC-MSCs effectively alleviate fulminant hepatitis in mouse models, primarily through inhibiting T cell immunity. RNA-sequencing of liver tissues and human T cells co-cultured with hUC-MSCs showed that NF-κB signaling and glycolysis are two main pathways involved in mediating the protective role of hUC-MSCs on both Con A-induced hepatitis in vivo and T cell activation in vitro. Conclusion: In summary, our data confirmed the potent therapeutic role of MSCs-derived from human umbilical cord on Con A-induced fulminant hepatitis, and uncovered new mechanisms that glycolysis metabolic shift mediates suppression of hUC-MSCs on T cell immunity.