Trained human bone marrow mesenchymal stem cells restore tissue immuno-microenvironment in fulminant hepatic failure mice

• Trained hBMSC (T-hBMSC) exhibit enhanced immunomodulatory and anti-inflammatory properties, with upregulation of PDL1 and IDO1, and downregulation of pro-inflammatory cytokines upon stimulation. • T-hBMSC transplantation significantly improves liver function (ALT, AST) and reduces inflammatory cytokines (IL6, MCP1) in fulminant hepatic failure (FHF) mice, leading to reduced necrosis and immune cell infiltration. • Transcriptomic analysis reveals that T-hBMSC shift the liver microenvironment from pro-inflammatory to regenerative, with downregulation of TNF/IL-17 signaling and upregulation of metabolic pathways. • T-hBMSC increase the proportion of anti-inflammatory F4/80+CD163+ macrophages in the liver, contributing to tissue immuno-microenvironment restoration and enhanced liver regeneration.