Sera from Patients with NMOSD Reduce the Differentiation Capacity of Precursor Cells in the Central Nervous System

Int J Mol Sci. 2021 May 14;22(10):5192. doi: 10.3390/ijms22105192.

Abstract

Introduction: AQP4 (aquaporin-4)-immunoglobulin G (IgG)-mediated neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disease that affects the central nervous system, particularly the spinal cord and optic nerve; remyelination capacity in neuromyelitis optica is yet to be determined, as is the role of AQP4-IgG in cell differentiation.

Material and methods: We included three groups-a group of patients with AQP4-IgG-positive neuromyelitis optica, a healthy group, and a sham group. We analyzed differentiation capacity in cultures of neurospheres from the subventricular zone of mice by adding serum at two different times: early and advanced stages of differentiation. We also analyzed differentiation into different cell lines.

Results and conclusions: The effect of sera from patients with NMOSD on precursor cells differs according to the degree of differentiation, and probably affects oligodendrocyte progenitor cells from NG2 cells to a lesser extent than cells from the subventricular zone; however, the resulting oligodendrocytes may be compromised in terms of maturation and possibly limited in their ability to generate myelin. Furthermore, these cells decrease in number with age. It is very unlikely that the use of drugs favoring the migration and differentiation of oligodendrocyte progenitor cells in multiple sclerosis would be effective in the context of neuromyelitis optica, but cell therapy with oligodendrocyte progenitor cells seems to be a potential alternative.

Keywords: AQP4–IgG; NMOSD; neural stem cells; neurogenesis; neuromyelitis optica; precursor cells; remyelination.

MeSH terms

  • Animals
  • Aquaporin 4 / immunology*
  • Autoantibodies / blood
  • Autoantibodies / immunology*
  • Case-Control Studies
  • Cell Differentiation*
  • Central Nervous System / immunology
  • Central Nervous System / pathology*
  • Cerebellum / immunology
  • Cerebellum / pathology
  • Female
  • Humans
  • Immunoglobulin G / immunology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Middle Aged
  • Neuromyelitis Optica / blood
  • Neuromyelitis Optica / immunology*
  • Neuromyelitis Optica / pathology
  • Oligodendrocyte Precursor Cells / immunology
  • Oligodendrocyte Precursor Cells / pathology*

Substances

  • AQP4 protein, human
  • Aquaporin 4
  • Autoantibodies
  • Immunoglobulin G