Abstract
Neurospheroids cultured from induced pluripotent stem cells (iPSC) represent an important research tool to study neuron-astrocyte interactions, during development, homeostasis and stress. In course of the EU MSCA ITN PMSMatTrain project, the UAntwerp partner developed a 5-week old murine iPSC-derived neurospheroid model containing mature neurons and astrocytes in order to evaluate the therapeutic potential of several neuro-protective/modulating compounds in vitro preceding animal experiments. Following development and characterization of this new murine iPSC-derived neurospheroid model, its sensitivity to immune signal-induced stress (a.o. stimulation with IL1b, TNF and/or LPS) has been demonstrated by monitoring astrocyte activation (a.o. production of IL6 and CXCL10). This SEP grant will be applied to support the 4th PhD year of Julia Di Stefano in which the candidate will investigate the neuro-protective/modulating activity of APRIL (delivered by means of AAV vectors) and placenta stem cell-derived factors (delivered by means of extracellular vesicles) on astrocyte activation in murine iPSC-derived neurospheroids. Finally, it is expected that the technology developed here will become an important additional tool in (i) fundamental research to study neuro-development and functioning, as well as (ii) to preselect interesting therapeutic molecules before proceeding to animal studies and/or human clinical trials.
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