Stem cell research & therapy · 2026
Adipose tissue-derived mesenchymal stem cells combined with prednisone synergistically ameliorate autoimmune hepatitis in mice.
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Kong Jinfeng, Liang Xiuhui, Chen Geng, Liu Xiaolong, Liao Naishun, Li Dongliang
Аннотация
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 abundance, and promoted regenerative signaling networks involving VEGF, TGF-β, and FGF pathways.
CONCLUSION: ADSCs combined with prednisone synergistically ameliorate immune-mediated liver injury through dual immunosuppression and modulation of key signaling pathways, promoting immune tolerance and tissue repair. This strategy offers a promising therapeutic approach for AIH.
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 abundance, and promoted regenerative signaling networks involving VEGF, TGF-β, and FGF pathways.
CONCLUSION: ADSCs combined with prednisone synergistically ameliorate immune-mediated liver injury through dual immunosuppression and modulation of key signaling pathways, promoting immune tolerance and tissue repair. This strategy offers a promising therapeutic approach for AIH.