Hepatorenal syndrome (HRS) is a severe complication of advanced liver disease with high mortality and limited treatment options, often requiring liver or combined liver-kidney transplantation. Current therapies fail to address the underlying multi-organ damage driven by necroptosis, systemic inflammation, and fibrosis. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have emerged as promising cell-free alternatives due to their immunomodulatory and regenerative properties, yet their potential in HRS remains unexplored.
Here, using a bile duct ligation-induced HRS mouse model, we demonstrate that intravenous administration of MSC-EVs significantly attenuates liver and kidney injuries. The treatment reduced hepatic necroptosis and renal tubular damage, downregulated IL-17 expression, and decreased fibrosis in both organs, leading to improved hepatic and renal function. Proteomic analysis revealed that MSC-EVs are enriched with proteins involved in renal protection, anti-fibrosis, and immune regulation, particularly IL-17 pathway modulation.
This work establishes MSC-EVs as an effective multi-target nanotherapy for HRS, acting through necroptosis inhibition, immune microenvironment reprogramming, and fibrosis resolution. The work, entitled “ Multiorgan Repair by MSC-Derived Extracellular Vesicles in Hepatorenal Syndrome through Necroptosis Alleviation, Immune Reprogramming and Fibrosis Resolution ”, was published on Extracellular Vesicles and Circulating Nucleic Acids (published on 12 Jan 2026).
Extracellular Vesicles and Circulating Nucleic Acids
Experimental study
Not applicable
Multiorgan repair by MSC-derived extracellular vesicles in hepatorenal syndrome through necroptosis alleviation, immune reprogramming and fibrosis resolution
12-Jan-2026