2. Academic Validation
  3. Umbilical Cord Mesenchymal Stromal Cell-Derived Extracellular Vesicles Transfer CD59 to Astrocytes to Alleviate Complement-Dependent Cytotoxicity

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

  • Mol Neurobiol. 2025 Nov 14;63(1):41. doi: 10.1007/s12035-025-05298-2.
Qi Shen # 1,  Xueying Wang # 1,  Qingjian Ou # 1,  Qian Wang 1,  Zhenzhen Zhao 1,  Zhiyang Chen 1,  Xiaoman Zhu 1,  Dongli Li 1,  Caixia Jin 1,  Furong Gao 1,  Juan Wang 1,  Lixia Lu 1,  Yanlong Bi 1,  Wenbin Wan 2,  Yangtai Guan 2,  Guo-Tong Xu # 3 4,  Jing-Ying Xu # 5,  Haibin Tian # 6 7
Affiliations

Affiliations

  • 1 Department of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, School of Medicine, Tongji University, Shanghai, 200065, China.
  • 2 Department of Neurology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
  • 3 Department of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, School of Medicine, Tongji University, Shanghai, 200065, China. [email protected].
  • 4 The Collaborative Innovation Center for Brain Science, Tongji University, Shanghai, 200092, China. [email protected].
  • 5 Department of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, School of Medicine, Tongji University, Shanghai, 200065, China. [email protected].
  • 6 Department of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, School of Medicine, Tongji University, Shanghai, 200065, China. [email protected].
  • 7 Department of Pharmacology, School of Medicine, Tongji University, Shanghai, 200092, China. [email protected].
  • # Contributed equally.
PMID: 41236660 DOI: 10.1007/s12035-025-05298-2
Abstract

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.

Keywords

Astrocyte; CD59; Complement-dependent cytotoxicity; Extracellular vesicle; Human umbilical cord-derived mesenchymal stromal cells.

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