Investigation of the role of platelets in the generation and maintenance of healthy myelin

"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."