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

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.

Ependyma: a new target for autoantibodies in neuromyelitis optica?

“… 48 Sera from NMO patients can enhance the production by SVZ neurospheres of GFAP + cells but reduce that of Tuj1 + (neurons) and Olig2 + (oligodendrocyte precursor cell). 37 Similarly, we found that NMO-IgG activates the proliferation of sub-ventricular cells and of qNSCs. NMO-IgG might have an effect not only directly on NSCs but also indirectly on targeting ependymocytes and astrocytes, leading to the release of inflammatory cytokines or transcription factors.…”

“… 16 , 17 However, the response of SV-NSCs is still unclear in NMO models. 37 Here, we evaluated the effects of NMO-IgG treatment during 24 hours on whole mount explant cultures. In the ependymal layer, quiescent neural stem cells (qNSCs) called B1 cells are able to produce precursors for neuroblasts and glial cells and project one process harbouring a single sensory cilium that is easily identified at the centre of ependymal surrounding pinwheels ( Fig.…”

Intranasal Administration of Undifferentiated Oligodendrocyte Lineage Cells as a Potential Approach to Deliver Oligodendrocyte Precursor Cells into Brain

“…However, there is a need for future studies addressing two main issues: firstly, whether these cells remain resident and in a quiescent state in OPC niches, their survival times and the factors involved in their survival, and the potential role of OPC-loaded microparticles; and secondly, the capacity of HOG cells to respond to such demyelinating diseases as multiple sclerosis [ 31 ] and neuromyelitis optica [ 84 ], degenerative diseases such as Alzheimer disease [ 85 ], trauma [ 86 ], vascular diseases, and primary diseases of myelin, such as Alexander disease [ 87 ]. Although the implanted HOG cells can proliferate and differentiate in vitro, questions remain on whether they behave similarly in vivo.…”

Remyelination in neuromyelitis optica spectrum disorder is promoted by edaravone through mTORC1 signaling activation

“…Because demyelination severely impacts axonal and neuronal functions (Liu et al, 2018; Papadopoulos & Verkman, 2012), remyelination has been suggested as a potential therapeutic target for NMOSD since remyelination can, in principle, rescue the functions in the injured areas of the CNS (Tradtrantip et al, 2020; Yao et al, 2016). However, several mechanisms may induce limited remyelination in NMOSD model that include inhibition of oligodendrocyte progenitor cell (OPC) differentiation into mature oligodendrocytes (OLs), inhibiting OPC migration through damaged BBB, changes in microglia that limit phagocytosis of myelin debris, or axonal alterations (Gómez‐Pinedo et al, 2021). Astrocyte play a significant role in trophic support to neuronal and glial cells, and alterations in astrocytes metabolism induce pathological conditions that lead to oligodendrocyte cell death and demyelination (Matute et al, 2007).…”