Genetically Engineered Artificial Microvesicles Carrying Nerve Growth Factor Restrains the Progression of Autoimmune Encephalomyelitis in an Experimental Mouse Model

Int J Mol Sci. 2023 May 5;24(9):8332. doi: 10.3390/ijms24098332.

Abstract

Multiple sclerosis (MS) is an incurable, progressive chronic autoimmune demyelinating disease. Therapy for MS is based on slowing down the processes of neurodegeneration and suppressing the immune system of patients. MS is accompanied by inflammation, axon-degeneration and neurogliosis in the central nervous system. One of the directions for a new effective treatment for MS is cellular, subcellular, as well as gene therapy. We investigated the therapeutic potential of adipose mesenchymal stem cell (ADMSC) derived, cytochalasin B induced artificial microvesicles (MVs) expressing nerve growth factor (NGF) on a mouse model of multiple sclerosis experimental autoimmune encephalomyelitis (EAE). These ADMSC-MVs-NGF were tested using histological, immunocytochemical and molecular genetic methods after being injected into the tail vein of animals on the 14th and 21st days post EAE induction. ADMSC-MVs-NGF contained the target protein inside the cytoplasm. Their injection into the caudal vein led to a significant decrease in neurogliosis at the 14th and 21st days post EAE induction. Artificial ADMSC-MVs-NGF stimulate axon regeneration and can modulate gliosis in the EAE model.

Keywords: ADMSC; MOG; NGF; artificial microvesicles; astrocytes; cytochalasin B; cytokines; demyelination; experimental autoimmune encephalomyelitis (EAE); lentivirus; multiple sclerosis; neurodegeneration.

MeSH terms

  • Animals
  • Axons / metabolism
  • Encephalomyelitis*
  • Encephalomyelitis, Autoimmune, Experimental* / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Multiple Sclerosis* / pathology
  • Nerve Growth Factor / genetics
  • Nerve Regeneration

Substances

  • Nerve Growth Factor

Grants and funding

This paper was supported by the Kazan Federal University Strategic Academic Leadership Program (PRIORITY-2030).