The liver, the body's nonstop 'chemical factory' for detoxification and metabolism, completely fails in ESLD, leading to extensive cell death, irreversible structural damage, and life-threatening complications. At present, liver transplantation remains the only curative option, but severe donor shortages and high costs leave countless patients waiting in suffering.
The number of patients with end-stage liver disease has been increasing continuously in recent years. Over 1.5 billion people suffer from liver disease, with end-stage cases often requiring transplants
Stem cells, as the body's 'repair toolkit', show therapeutic potential for liver disease by differentiating into liver cells, but direct injection may risk tumorigenesis.
Cirrhosis arises when hepatic stellate cells become abnormally activated, functioning as unchecked “collagen factories” that overproduce fibers, gradually replacing normal tissue with rigid scar, impairing liver structure and function.
Current approaches using single effector molecules from stem cell exosomes show limited efficacy; moreover, they often trigger compensatory responses in liver tissue, undermining therapeutic outcomes and failing to provide sustained, robust antifibrotic effects.
High Cost
Organ Shortage
Graft Rejection
Exosomes are nanoscale extracellular vesicles released by most cell types, containing proteins, lipids, and nucleic acids. They mediate intercellular communication and are increasingly recognized as biomarkers and potential therapeutic agents.
Benefits of Exosomes: Exosomes, carrying proteins and mRNA, promote liver cell regeneration, improve the liver microenvironment, suppress hepatic stellate cell activation, and reverse fibrosis.
This project proposes an engineered exosome therapy by modifying mesenchymal stem cells to efficiently load synergistic therapeutic miRNAs. The dual delivery of miR-455-3p and miR-148a-5p targets HSCs to reduce fibrosis markers while boosting anti-inflammatory factors like IL-10, further enhancing therapeutic efficacy.
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