Adipose tissue-derived mesenchymal stem cells combined with prednisone synergistically ameliorate autoimmune hepatitis in mice.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Background The combination of adipose tissue-derived mesenchymal stem cell (ADSC) transplantation with conventional therapy for autoimmune hepatitis (AIH) represents a critical step toward the clinical translation of ADSC-based therapeutics. However, no preclinical studies have yet reported on such combination therapy for AIH. This study aims to evaluate the therapeutic efficacy of ADSC-prednisone (AP) combined therapy in an AIH mouse model and to investigate the underlying mechanisms. Methods ConA-induced and CFA/S100-induced AIH mice were treated with prednisone, ADSCs, or AP combination therapy. Serum biochemistry, histopathology, immune cell infiltration, cytokine profiles, MAPK signaling pathways (p38/MAPK, JNK/ERK), and single-cell RNA sequencing (scRNA-seq) were analyzed. Results Both ADSC and prednisone monotherapies significantly reduced serum transaminases (ALT, AST, ALP, TBIL) and hepatic inflammation compared with untreated controls. Notably, AP combination therapy demonstrated superior protection, with greater reductions in immune cell infiltration (CD4⁺, CD8⁺, CD11b⁺), pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, IL-12), and autoantibody production (IgG). Mechanistically, ADSCs suppressed p38/MAPK activation, while AP further enhanced inhibition of JNK/p38 signaling. scRNA-seq revealed that AP therapy reshaped the liver cellular landscape, reduced immune cell a

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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