Mesenchymal stem cell alleviate concanavalin A-induced hepatitis via immune reprogramming and complement regulation

BackgroundConcanavalin A (ConA)-induced acute hepatitis is a widely used murine model for studying immune-mediated liver injury, characterized by T-cell activation and pro-inflammatory cytokine production. Mesenchymal stem cells (MSCs) have shown promise in mitigating liver injury through immunomodulation, but the precise cellular and molecular mechanisms remain unclear.

This study leverages single-cell RNA sequencing (scRNA-seq) to elucidate the role of MSCs in reshaping the hepatic immune microenvironment during acute liver injury.MethodsSingle-cell suspensions were isolated from liver tissues of ConA-induced acute hepatitis mice, with or without MSC treatment. ScRNA-seq libraries were generated using the 10× Genomics platform, and data were processed using Seurat for quality control, clustering, and cell-type annotation.

Trajectory and pseudotime analysis were performed using Monocle 3 to model differentiation pathways. Ligand-receptor interactions were analyzed using CellChat to identify active signaling pathways.

Key findings were further assessed in situ by multiplex immunohistochemistry (mIHC).ResultsMSC administration markedly alleviated ConA-induced acute liver injury. scRNA-seq analysis showed that the global hepatic cellular landscape remained largely dominated by the acute inflammatory challenge, whereas MSC treatment was associated with selective remodeling of specific immune compartments.