Abstract
Due to the enormous impact of stroke on the patient's quality of life and on society, decades of research resulted in the identification of thousands of candidate neuroprotective drugs. Unfortunately, none have led to an effective therapy to date. This can partially be attributed to the lack of in vitro systems able to accurately recapitulate human ischemic responses. Fortunately, the advent of induced pluripotent stem cell (iPSC)-technology has provided novel tools for generating human-based in vitro brain models, namely neurospheroids. Extending the host laboratories' preceding research efforts to generate bi-partite (neurons + astrocytes) and tri-partite (neurons + astrocytes + microglia) human iPSC-derived neurospheroids, I hypothesize that subjection of mature tri-partite neurospheroids to stroke-like conditions (oxygen/glucose-deprivation), in combination with advanced single cell analysis tools and measurement of electrophysiological network activity, will aid to unravel biologically relevant cellular and molecular events in the context of stroke pathology. In this way, the combined cellular and molecular toolbox for neurospheroid culture, manipulation and analysis will in short term pave the way for novel fundamental studies unravelling new pathways and/or potential targets for neuroprotection or repair, and in long-term novel therapeutic approaches for patients with cerebral ischemia.
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