<p>Spinal cord injury (SCI) causes severe functional impairments and involves both primary mechanical damage and secondary inflammation. Exosomes from human umbilical cord blood (HUCB) are emerging as promising therapies due to their bioactive components that regulate inflammation and support repair. Thirty-two male rats were randomly divided into four groups: Group A (laminectomy), Group B (contusion), Group C (contusion + PBS), and Group D (contusion + HUCB-exosomes). Contusion injuries were induced using the New York University (NYU) impactor method. HUCB-derived exosomes were extracted and confirmed using scanning electron microscopy (SEM), transmission electron microscopy (TEM), surface markers CD81 and CD9 via flowcytometry, along with dynamic light scattering (DLS), and zeta potential analysis. HUCB-exosomes were administered without prior in vitro expansion; 30 minutes’ post-injury, Group D received 100&#xa0;µg of HUCB-exosomes via tail vein injection for one week. Motor and behavioral functions were assessed using the Basso, Beattie, and Bresnahan (BBB) scale, narrow beam test (NBT), rotarod test, and open-field test. Western blotting was performed eight weeks’ post-injury to analyze changes in inflammatory cytokines, and histological changes were assessed via H&amp;E staining. HUCB-exosome administration significantly enhanced functional recovery in SCI rats, as evidenced by higher BBB scores, improved narrow beam, rotarod, and open-field performances compared with PBS and contusion groups. Histological analysis showed reduced cavity formation, increased neuronal density, and decreased gliosis in the exosome-treated group. Western blot results revealed marked downregulation of TNF-α, NLRP3, and GFAP expression. Additionally, exosome therapy restored antioxidant balance by reducing ROS and GSSG levels while elevating GSH, and immunohistochemistry confirmed reduced expression of apoptotic and autophagy markers. This study highlights the therapeutic potential of HUCB-derived exosomes in SCI, demonstrating their ability to attenuate inflammation and promote functional recovery. These findings support HUCB-exosomes as a promising, non-cell-based treatment strategy for SCI.</p>

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Human umbilical cord plasma derived exosome inhibit the NLRP3 inflammasome and neuro-apoptosis in traumatic spinal cord injury model

  • Hadise Taheri,
  • Hamid Reza Mosleh,
  • Leila Darabi,
  • Shima Jahanbaz,
  • Hooman Kazemi Mirni,
  • Reza Mastery Farahani,
  • Abbas Aliaghaei,
  • Hamid Nazarian,
  • Reza Bahar,
  • Maral Hasanzadeh,
  • Foozhan Tahmasebinia,
  • Amirreza Beirami,
  • Hojjat-Allah Abbaszadeh,
  • Shahram Darabi

摘要

Spinal cord injury (SCI) causes severe functional impairments and involves both primary mechanical damage and secondary inflammation. Exosomes from human umbilical cord blood (HUCB) are emerging as promising therapies due to their bioactive components that regulate inflammation and support repair. Thirty-two male rats were randomly divided into four groups: Group A (laminectomy), Group B (contusion), Group C (contusion + PBS), and Group D (contusion + HUCB-exosomes). Contusion injuries were induced using the New York University (NYU) impactor method. HUCB-derived exosomes were extracted and confirmed using scanning electron microscopy (SEM), transmission electron microscopy (TEM), surface markers CD81 and CD9 via flowcytometry, along with dynamic light scattering (DLS), and zeta potential analysis. HUCB-exosomes were administered without prior in vitro expansion; 30 minutes’ post-injury, Group D received 100 µg of HUCB-exosomes via tail vein injection for one week. Motor and behavioral functions were assessed using the Basso, Beattie, and Bresnahan (BBB) scale, narrow beam test (NBT), rotarod test, and open-field test. Western blotting was performed eight weeks’ post-injury to analyze changes in inflammatory cytokines, and histological changes were assessed via H&E staining. HUCB-exosome administration significantly enhanced functional recovery in SCI rats, as evidenced by higher BBB scores, improved narrow beam, rotarod, and open-field performances compared with PBS and contusion groups. Histological analysis showed reduced cavity formation, increased neuronal density, and decreased gliosis in the exosome-treated group. Western blot results revealed marked downregulation of TNF-α, NLRP3, and GFAP expression. Additionally, exosome therapy restored antioxidant balance by reducing ROS and GSSG levels while elevating GSH, and immunohistochemistry confirmed reduced expression of apoptotic and autophagy markers. This study highlights the therapeutic potential of HUCB-derived exosomes in SCI, demonstrating their ability to attenuate inflammation and promote functional recovery. These findings support HUCB-exosomes as a promising, non-cell-based treatment strategy for SCI.