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<p>The retinal astrocyte death induced by complement-dependent cytotoxicity (CDC) is the major etiology of retinal injury in patients with neuromyelitis optica spectrum disorders (NMOSD). Human umbilical cord-derived mesenchymal stromal cells (hUCMSCs) and their derived extracellular vesicles (EVs) have emerged as a potential therapeutic option due to their immunomodulatory capabilities. This study is aimed at establishing a serum-free culture system for hUCMSCs (SF-UCMSCs) and investigating the inhibiting effect of EVs derived from SF-UCMSCs on CDC-induced retinal astrocyte death. The results showed that SF-UCMSCs retained canonical mesenchymal stromal cells’ characteristics under serum-free culture conditions. Pharmacokinetic analysis showed that intravenously administered SF-UCMSCs predominantly accumulated in the lungs, liver, spleen, and kidneys, with no detectable localization in the retina. Notably, EVs derived from SF-UCMSCs exerted a protective effect against CDC-mediated damage to murine retinal astrocytes, as evidenced by reduced formation of C5b-9 + membrane attack complexes and diminished astrocyte death. Mechanistically, this protective effect was associated with the transfer of CD59 from EVs to astrocytes. In summary, the establishment of this serum-free culture system facilitates the development of hUCMSC-derived EVs as therapeutic agents, circumventing the risks of immune rejection and potential tumorigenicity associated with cellular transplantation. This study also provides a mechanistic basis and therapeutic strategy for managing autoimmune diseases characterized by CDC-mediated pathogenesis.</p>

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Umbilical Cord Mesenchymal Stromal Cell-Derived Extracellular Vesicles Transfer CD59 to Astrocytes to Alleviate Complement-Dependent Cytotoxicity

  • 期刊论文

  • 发表日期：

    2025年11月14日

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  • Qi Shen,
  • Xueying Wang,
  • Qingjian Ou,
  • Qian Wang,
  • Zhenzhen Zhao,
  • Zhiyang Chen,
  • Xiaoman Zhu,
  • Dongli Li,
  • Caixia Jin,
  • Furong Gao,
  • Juan Wang,
  • Lixia Lu,
  • Yanlong Bi,
  • Wenbin Wan,
  • Yangtai Guan,
  • Guo-Tong Xu,
  • Jing-Ying Xu,
  • Haibin Tian

摘要

The retinal astrocyte death induced by complement-dependent cytotoxicity (CDC) is the major etiology of retinal injury in patients with neuromyelitis optica spectrum disorders (NMOSD). Human umbilical cord-derived mesenchymal stromal cells (hUCMSCs) and their derived extracellular vesicles (EVs) have emerged as a potential therapeutic option due to their immunomodulatory capabilities. This study is aimed at establishing a serum-free culture system for hUCMSCs (SF-UCMSCs) and investigating the inhibiting effect of EVs derived from SF-UCMSCs on CDC-induced retinal astrocyte death. The results showed that SF-UCMSCs retained canonical mesenchymal stromal cells’ characteristics under serum-free culture conditions. Pharmacokinetic analysis showed that intravenously administered SF-UCMSCs predominantly accumulated in the lungs, liver, spleen, and kidneys, with no detectable localization in the retina. Notably, EVs derived from SF-UCMSCs exerted a protective effect against CDC-mediated damage to murine retinal astrocytes, as evidenced by reduced formation of C5b-9 + membrane attack complexes and diminished astrocyte death. Mechanistically, this protective effect was associated with the transfer of CD59 from EVs to astrocytes. In summary, the establishment of this serum-free culture system facilitates the development of hUCMSC-derived EVs as therapeutic agents, circumventing the risks of immune rejection and potential tumorigenicity associated with cellular transplantation. This study also provides a mechanistic basis and therapeutic strategy for managing autoimmune diseases characterized by CDC-mediated pathogenesis.