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).
DOI: 10.20517/evcna.2025.99