# Platelets During Myelin Repair in Multiple Sclerosis: Friend or Foe?

## TL;DR

The paper explores how platelets influence remyelination in multiple sclerosis, suggesting they can both support and hinder the process.

## Contribution

The study reveals a complex role of platelets in remyelination and provides new insights for MS treatment strategies.

## Key findings

- Platelet depletion reduces oligodendrocyte progenitor cell differentiation, hindering remyelination.
- Transient platelet exposure boosts OPC differentiation, but sustained exposure suppresses it.
- In MS and EAE, platelets aggregate in lesions and become hyperactive, contributing to remyelination failure.

## Abstract

Multiple sclerosis (MS) is an autoimmune neuroinflammatory demyelinating disease of the central nervous system (CNS) that affects more than 2.5 million people worldwide. Remyelination represents a robust regenerative response to myelin damage; however, during the later stages of MS, this process largely fails. Upon demyelination, oligodendrocyte progenitor cells (OPCs) proliferate, migrate, and differentiate into mature remyelinating oligodendrocytes. Why does remyelination fail in MS? Platelets are small, oval, anucleate cells that circulate in the bloodstream and form a hemostatic plug to stop blood leakage upon endothelial damage. Platelet function is not restricted to hemostasis; they also display tissue‐regenerative activities. Here, we review evidence suggesting that platelets act as modulators of OPC function during remyelination. Additionally, we describe platelet alterations associated with MS that may contribute to remyelination failure. Finally, we highlighted our previous study that addressed these issues. This study showed that in response to myelin damage, platelets transiently accumulate within the lesion. Interestingly, platelet depletion leads to a reduction in OPC differentiation, hindering remyelination. In vitro studies revealed that transient exposure to platelets boosts OPC differentiation, whereas sustained exposure to platelets suppresses this beneficial effect. Consistent with this observation, in an in vivo model of thrombocytosis (Calr+/−
), we found a sustained increase in the number of blood‐borne platelets recruited into the CNS (as observed in MS lesions), resulting in a significant decline in OPC differentiation during remyelination. These findings reveal a complex role of platelets in remyelination and provide new insights for understanding the MS pathology as well as for designing regenerative strategies for the treatment of this disease.

Platelets support remyelination, while alterations in their function in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) may contribute to remyelination failure. In healthy individuals, platelet function encompasses roles in hemostasis, inflammation, and tissue regeneration, among others. Recent findings indicate that platelets play a crucial role in oligodendrocyte progenitor cell (OPC) differentiation and remyelination. However, in the context of MS and EAE, platelets aggregate in chronic non‐remyelinated lesions, become hyperactive, and exhibit increased adhesiveness. MS patients show an increase in circulating platelet microparticles, while EAE animal models display elevated circulating platelet numbers. These observations, along with recent findings, suggest that alterations in platelet function may contribute to remyelination failure in MS.