Human iPSC Derived Microglia Cell Assays


K Shea1; E Offer1; G Marshall1; R Kelly1; E jones1; A Rutkowski1; P Simpson1
1 Medicines Discovery Catapult, UK


•Microglia are the resident immune cell of the central nervous system (CNS) and pivotal to the neuroinflammatory response and protection of neuronal function.

•The cells make up 10-20% of the cells of the CNS and in a resting state survey their microenvironment for threats to homeostasis within the neuronal microenvironment that would interfere with neuronal function. This homeostasis can be disrupted by bodies such as protein aggregates and apoptotic neurons, leading to both acute and chronic neuroinflammation.

•Microglia are activated following the detection of a threat to this homeostasis and undergo a number of phenotypic responses (cell migration, proliferation, cytokine release and phagocytosis), preventing change to the homeostasis within the neuronal microenvironment and associated detrimental effects on neuronal functional.

•The ability of microglial to detect and respond to aggregated proteins (E.g. β-Amyloid plaques, Lewy bodies/α-synuclein) or apoptotic neurons is important in the pathogenesis of a range of neurodegenerative diseases like Alzheimer’s Disease, Motor Neurone Disease and Parkinson’s Disease.

•This work describes the use of iPSC derived microglia to develop cell models to functionally characterise a range of phenotypic activities (cytokine release, phagocytotic activity and cell migration) in vitro.

•The ability to measure these functions in a lab will allow us to expedite the development of more clinically predictive disease relevant human cell models for a range of neurodegenerative diseases with the aim of identifying more effective treatments any improved model will bring.

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