Circulating platelets modulate oligodendrocyte progenitor cell differentiation during remyelination
Revealing unknown cues that regulate oligodendrocyte progenitor cell (OPC) function in remyelination is important to optimise the development of regenerative therapies for multiple sclerosis (MS). Platelets are present in chronic non-remyelinated lesions of MS and an increase in circulating platelets has been described in experimental autoimmune encephalomyelitis (EAE) mice, an animal model for MS. However, the contribution of platelets to remyelination remains unexplored. Here we show platelet aggregation in proximity to OPCs in areas of experimental demyelination. Partial depletion of circulating platelets impaired OPC differentiation and remyelination, without altering blood-brain barrier stability and neuroinflammation. Transient exposure to platelets enhanced OPC differentiation in vitro, whereas sustained exposure suppressed this effect. In a mouse model of thrombocytosis ( Calr +/- ), there was a sustained increase in platelet aggregation together with a reduction of newly-generated oligodendrocytes following toxin-induced demyelination. These findings reveal a complex bimodal contribution of platelet to remyelination and provide insights into remyelination failure in MS.
Authors
- Khalil S. Rawji (ORCID: https://orcid.org/0000-0002-9687-8330)
- Robin J.M. Franklin (ORCID: https://orcid.org/0000-0001-6522-2104)
- Ginez A. Gonzalez Martinez
- Ilias Kazanis (ORCID: https://orcid.org/0000-0003-1035-0584)
- Penelope Dimas (ORCID: https://orcid.org/0000-0002-5941-4828)
- Maria Elena Silva (ORCID: https://orcid.org/0000-0001-6236-7180)
- Cédric Ghevaert (ORCID: https://orcid.org/0000-0002-9251-0934)
- Josselyne Mansilla
- Chao Zhao (ORCID: https://orcid.org/0000-0003-1144-1621)
- Carolina R. Reyes (ORCID: https://orcid.org/0000-0002-9005-0313)
- Amie K. Waller (ORCID: https://orcid.org/0000-0002-9726-5560)
- Maite A. Castro (ORCID: https://orcid.org/0000-0003-2526-0485)
- Francisco J. Rivera (ORCID: https://orcid.org/0000-0001-7895-6318)
- Bryan Hinrichsen
- César Ulloa-Leal (ORCID: https://orcid.org/0009-0005-7750-0382)
- Ludwig Aigner (ORCID: https://orcid.org/0000-0002-1653-8046)
- Pamela Ehrenfeld (ORCID: https://orcid.org/0000-0002-2519-7570)
- Amber R. Philp (ORCID: https://orcid.org/0000-0001-6380-6851)
- Carlos Valenzuela‐Krugmann (ORCID: https://orcid.org/0009-0007-4825-5802)
- Amar Sharma (ORCID: https://orcid.org/0009-0001-7737-6466)
- Diana M Bessa de Sousa
Institutions
- NHS Blood and Transplant (GB)
- University of Helsinki (FI)
- Austral University of Chile (CL)
- Wellcome/MRC Cambridge Stem Cell Institute (GB)
- University of Cambridge (GB)
- Paracelsus Medical University (AT)
- Viña del Mar University (CL)
- University of Westminster (GB)
Publication Details
- Journal
- eLife
- Published
- 2024-08-20
- DOI
- https://doi.org/10.7554/elife.91757.3
- Primary Topic
- Extracellular vesicles in disease
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Agencia Nacional de Investigación y Desarrollo