SP 7.13 Engineered Exosomes from Umbilical Cord Mesenchymal Stem Cells with pPB Modification Attenuate Hepatic Fibrosis via Hepatic Stellate Cell Targeting

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ID: 324079
2026
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Abstract
Abstract Background Current therapies for hepatic fibrosis remain inadequate due to the lack of safe, selective targeting of activated hepatic stellate cells (aHSCs). Although hUCMSC-derived exosomes show antifibrotic potential, their efficacy is limited by rapid MPS clearance and poor specificity. This study engineered surface-modified exosomes to enhance aHSC targeting and improve antifibrotic performance. Methods and results We engineered a targeted exosomal delivery system by decorating hUCMSC-derived exosomes with the pPB cyclic peptide (hUCMSC-Exos@pPB) using DSPE-PEG-NH₂–mediated nano-assembly, enabling selective recognition of activated hepatic stellate cells (aHSCs). Targeting specificity was evaluated through in vivo fluorescence imaging and α-smooth muscle actin (α-SMA) co-localization analyses. The biosafety of hUCMSC-Exos@pPB was rigorously assessed via CCK-8 cytotoxicity assays, histological examination of major organs, and measurements of liver and renal function biomarkers. The anti-fibrotic efficacy of hUCMSC-Exos@pPB was examined using complementary approaches, including histopathological staining (H&E, Masson, Sirius Red), assessment of oxidative stress indicators (malondialdehyde, NADPH oxidase 4), serum liver function tests (AST, ALT), and evaluation of fibrogenic protein expression (α-SMA, COL1a1) in vivo and in HSC-T6 cells. Transcriptomic RNA-seq analysis of liver tissue further identified the PI3K–Akt signaling pathway as a key mechanism underlying the anti-fibrotic actions of hUCMSC-Exos@pPB. Conclusion Through rational pPB ligand–based surface engineering, we developed an exosomal nanoplatform that efficiently evades MPS clearance and achieves precise targeting of activated hepatic stellate cells. This strategy markedly enhances the antifibrotic efficacy of hUCMSC-Exos, providing a promising translational avenue for precision therapy in hepatic fibrosis.
Reference Key
openalex_W7172505954 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Fanghong Wang, Fanghui Ding, Jianling Zhang, Xiaoliang Zhu, 朱克祥, xun li
Journal the british journal of surgery
Year 2026
DOI
10.1093/bjs/znag087.097
URL
https://doi.org/10.1093/bjs/znag087.097
Keywords Keywords not found

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