Dual-mode action of scalable, high-quality engineered stem cell-derived SIRPα-extracellular vesicles for treating acute liver failure.

ABSTRACT: Acute liver failure (ALF) is a life-threatening condition caused by rapid hepatocyte death and impaired liver regeneration. Here we show that extracellular vesicles engineered to express Signal Regulatory Protein Alpha (SIRP-EVs), produced via a scalable 3D bioreactor process with high yield and purity, exhibit significant therapeutic potential by targeting damaged cells and promoting tissue repair. SIRP-EVs block CD47, a crucial inhibitory signal on necroptotic cells, to enhance macrophage-mediated clearance of dying hepatocytes. They also deliver regenerative cargo from mesenchymal stem cells, reprogramming macrophages to support liver regeneration. In male animal models, SIRP-EVs significantly reduce liver injury markers and improve survival, demonstrating their dual-function therapeuti

SUBMITTER: Kim S 

PROVIDER: S-EPMC11847939 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature