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<p>Epidural fibrosis (EF) is a frequent and debilitating complication that impairs recovery following spinal surgery, yet effective targeted therapies are lacking. Here we observe enrichment of FAP⁺ fibroblasts at surgical sites in patients after laminectomy. To therapeutically target this subset, we develop bispecific antibody–decorated extracellular vesicles (BsAb EVs), which redirect endogenous T cells to eliminate FAP⁺ fibroblasts in situ. In a preclinical model, BsAb EVs selectively eliminate pathogenic fibroblasts, reduce fibrotic collagen accumulation, and prevent the development of postoperative epidural fibrosis without detectable systemic toxicity under the tested conditions. Single-cell RNA sequencing reveals that FAP⁺ fibroblasts represent a transcriptionally distinct subset from α-SMA⁺ myofibroblasts, characterized by enhanced extracellular matrix remodeling and TGF-β production. Together, these findings highlight a critical stromal subset in EF pathogenesis and position BsAb EVs as a promising immunotherapeutic strategy for targeting pathogenic stromal cells in fibrotic and tissue-remodeling disorders.</p>

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Bispecific antibody engineered extracellular vesicles redirect T cells to prevent postoperative epidural fibrosis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月27日

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  • Shanwei Ye,
  • Qian Xu,
  • Yong Xu,
  • Hui Lu,
  • Zhenfeng Liu,
  • Jianfeng Guo,
  • Yichuan Li,
  • Wei Wang,
  • Jun Ran,
  • Xiaohua Zhu,
  • Dongling Zhu,
  • Wei Wu,
  • Zechuan Yang,
  • Shiqi Gu,
  • Feng Li,
  • Lugui Qiu,
  • Ellen Puré,
  • Vijay G. Bhoj,
  • Liang Huang,
  • Wei Xiong,
  • Zheng Zhang

摘要

Epidural fibrosis (EF) is a frequent and debilitating complication that impairs recovery following spinal surgery, yet effective targeted therapies are lacking. Here we observe enrichment of FAP⁺ fibroblasts at surgical sites in patients after laminectomy. To therapeutically target this subset, we develop bispecific antibody–decorated extracellular vesicles (BsAb EVs), which redirect endogenous T cells to eliminate FAP⁺ fibroblasts in situ. In a preclinical model, BsAb EVs selectively eliminate pathogenic fibroblasts, reduce fibrotic collagen accumulation, and prevent the development of postoperative epidural fibrosis without detectable systemic toxicity under the tested conditions. Single-cell RNA sequencing reveals that FAP⁺ fibroblasts represent a transcriptionally distinct subset from α-SMA⁺ myofibroblasts, characterized by enhanced extracellular matrix remodeling and TGF-β production. Together, these findings highlight a critical stromal subset in EF pathogenesis and position BsAb EVs as a promising immunotherapeutic strategy for targeting pathogenic stromal cells in fibrotic and tissue-remodeling disorders.