Project description
How blood platelets influence myelin health in the ageing brain
Platelets – tiny blood cells best known for sealing wounds – are increasingly recognised as modulators of inflammation and tissue regeneration. Emerging evidence suggests that platelets infiltrating the central nervous system through microscopic bleeds affect myelin-generating cells with impact on neuronal protection and connectivity. Small numbers are beneficial but prolonged or excessive presence can be detrimental to myelin, with direct relevance to ageing, multiple sclerosis and vascular dementia. With the support of the Marie Skłodowska-Curie Actions programme, the HealthyMyelin project aims to define precisely how human platelets influence myelin generation and maintenance using co-cultures and spinal cord organoids, exploring whether effects require direct cell contact or are mediated by extracellular vesicles.
Objective
"Platelets are numerous, small, anucleate, cells that circulate in blood vessels, typically considered only necessary for the formation of plugs in areas of vascular injury. However, accumulating experimental and clinical evidence has revealed that they can also modulate inflammation and regeneration. Previous experimental work of the supervisor's lab has shown that when platelets find their way in the central nervous system (CNS), they affect neural stem and progenitor cells, especially those gnerating myelin, the sheath that protects neurons and contributes to neuronal connectivity. In small numbers they create supportive microenvironments, but they become detrimental to myelin generation and regeneration when their numbers and the duration of their presence increases.
The appearance of brain micro-bleedings (leading to local infiltration of platelets) and of myelin degeneration is a frequent finding in the ageing CNS and in a range of brain neuropathologies, including vascular dementia and multiple sclerosis. Interestingly, immune thrombocytopenia (ITP), in which numbers of platelets are low, is also characterised by microbleedings and is correlated to cognitive decline.
In this project the fellow will built on her experience on working with mouse neural stem/ progenitor cells and platelets, to setup co-cultures of human platelets with human neural progenitors and spinal cord organoids. By collaborating with researchers at the Universities of Westminster and of Cambridge she will: a) define the parameters (numbers and time) that make platelets detrimental to the generation and the maintenance of healthy myelin in the human CNS. b) Explore if these effects necessitae the direct contact between platelets and myelin, or are mediated by diffusible microparticles, called extracellular vesicles. c) Assess if platelets colleted by ""older"" donors or by ITP patients show altered effects that contribute to pathology."
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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(opens in new window) HORIZON-MSCA-2025-PF
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W1B 2UW LONDON
United Kingdom
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