Continuous Immune-Modulatory Effects of Human Olig2+ Precursor Cells Attenuating a Chronic-Active Model of Multiple Sclerosis

Oligodendrocyte progenitor cells differentiation induction with MAPK/ERK inhibitor fails to support repair processes in the chronically demyelinated CNS

“…As OPC immune functions may have a role in their regenerative capacity, we examined whether they are impaired by PD0325901. We have previously shown in a co‐culture assay that OPC possess immune‐modulatory properties, by which they partially limit the activation and proliferation of LNCs following stimulation with ConA or myelin‐specific autoantigens (Nishri et al, 2020; Zveik, Fainstein, et al, 2022). Therefore, we used this assay to examine the effects of PD0325901 on OPC‐immune cell interactions.…”

“…However, it is now accepted that OPCs also have immunomodulatory functions and may play a prominent role as part of the immune milieu of the CNS (Akay et al, 2021; Boccazzi et al, 2022; Falcão et al, 2018). It was shown that OPC can secrete cytokines and chemokines such as CCL2 and TNFa in response to injury (Moyon et al, 2015; Zveik, Fainstein, et al, 2022), they can present antigen via major histocompatibility complex (MHC)‐I and ‐II (Falcão et al, 2018; Kirby et al, 2019; Zveik, Fainstein, et al, 2022), affect T cell activation and proliferation (Falcão et al, 2018; Nishri et al, 2020; Zveik, Fainstein, et al, 2022), and internalize myelin debris through phagocytosis (Falcão et al, 2018). Furthermore, it has been suggested that oligodendroglia are pre‐programmed at the chromatin level and can rapidly activate an immune response in the context of disease (Meijer et al, 2020).…”

Lumbar spine intrathecal transplantation of neural precursor cells promotes oligodendrocyte proliferation in hot spots of chronic demyelination

“…The morphometric analysis enabled us to identify normal and normal appearing (preserved) axons, dystrophic, with onion‐like appearance degenerated fibers, completely denuded axons (demyelinated), and small‐caliber fibers with thin myelin sheaths mainly found in the most superficial tracts of white matter [50]. We postulate that the proliferative host oligodendrocytes, the parenchymal NPCs, and even up to a degree the subarachnoid NPCs—mainly because of the spatial continuity to subpial layers—shifted the g‐ratio, which practically translates to clinical rehabilitation [51, 52]. This location‐based neuroprotective effect has been also achieved in experimental SCI [36].…”

Cell‐based experimental strategies for myelin repair in multiple sclerosis

“…Other combinatorial approaches could hold promise for repair- Kim et al, 2012;Chen et al, 2014;Nishri et al, 2020;Shen et al, 2006 Human and mouse iPSC-derived NPCs Cuprizone and shiverer mice: remyelination. > survival.…”

“…Cell treatment was associated with an increase in the number of Foxp3 + regulatory T cells within the spinal cord at 5 days after transplantation, and with the retention of inflammatory cells within the subarachnoid space. Nishri et al intracerebrally injected hESC‐derived NPCs into a chronic‐active mouse model of MS, at 30 days after EAE induction (Nishri et al, 2020). This treatment reduced disease parameters, and also neuroinflammation, demyelination, and axonal loss as compared to control EAE mice.…”