Abstract
BackgroundFulminant hepatitis is a severe life-threatening clinical condition with rapid progressive loss of liver function. It is characterized 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. Transplantation of MSCs is suggested as a promising therapeutic approach for a host of inflammatory conditions.MethodsIn 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 Wharton's jelly-derived MSCs (hWJ-MSCs) on fulminant hepatitis.ResultsWe showed that hWJ-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 hWJ-MSCs showed that NF-κB signaling and glycolysis are two main pathways mediating the protective role of hWJ-MSCs on both Con A-induced hepatitis in vivo and T cell activation in vitro.ConclusionIn summary, our data confirmed the potent therapeutic role of MSCs-derived from Wharton's jelly of human umbilical cord on Con A-induced fulminant hepatitis, and uncovered new mechanisms that glycolysis metabolic shift mediates suppression of T cell immunity by hWJ-MSCs.
Highlights
Fulminant hepatitis is a severe life-threatening clinical condition with rapid progressive loss of liver function
Concanavalin A (Con A)-induced fulminant liver injury is a well-documented murine model closely resembling the pathological process of human viral hepatitis and autoimmune liver disease [20,21,22,23]
Results hWJ‐Mesenchymal stem cells (MSCs) effectively protected mice from Con A‐induced fulminant hepatitis Like MSCs of other origins and previous reports [2, 3], hWJ-MSCs were strongly positive for CD29, CD73, CD105, and CD90, whereas negative for hematopoietic stem cell markers such CD34 and CD45 (Additional file 1: Figure S1A)
Summary
Fulminant hepatitis is a severe life-threatening clinical condition with rapid progressive loss of liver function. There are sufficient sources (based on the common cell dose frequently administered to the afore-mentioned disorders (1*106 cells/kg of body weight), the amount of hWJ-MSCs isolated from a single donor are frequently sufficient to treat 30 patients), suitable materials, easy isolation and culture procedures, and no ethical or moral restrictions for utilizing hWJ-MSCs [36]. These advantages make hWJ-MSCs an attractive option for stem cell-based therapy
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