Generation of iPSC-derived 3D neuro-immune cell culture models for study and modulation of neuro-inflammatory processes.

Development of three-dimensional (3D) in vitro cell culture models for neuroscience research is currently a hot topic in medical cell biology research. Although multiple protocols have been described for generating 3D brain organoids starting from pluripotent stem cells, current models display several limitations, including the lack of extracellular matrix (ECM) and the absence of glial and immune cells. With this project we aim to develop and optimize a new method for generating 3D neuro-immune cell culture models to study and modulate neuro-inflammatory responses. For this, 3D cell cultures comprising induced pluripotent stem cell (iPSC)-derived neurons, astrocytes and microglia will be established on decellularized mouse brain sections in order to provide growth and organizational support by the original brain ECM. Further inclusion of genetic engineering strategies, to allow for real time bioluminescence imaging and live cell confocal microscopy, will be applied to ensure high throughput screening applications. Once established, we will use this technology to further extend our research efforts to optimize therapeutic strategies based on interleukin (IL)13-mediated immunomodulation, following hypoxic and hypoglycemic stress. Once validated, we believe that implementation of this technology by pharmaceutical industry will have great impact on the reliability of pre-clinical drug screening, and consequently on the medical and social investments associated with patient care.

Keywords:STEM CELL PHYSIOLOGY, CELL CULTURES, 3D MICROSCOPY, STEM CELLS

Disciplines:Biomarker discovery and evaluation, Drug discovery and development, Medicinal products, Pharmaceutics, Pharmacognosy and phytochemistry, Pharmacology, Pharmacotherapy, Toxicology and toxinology, Other pharmaceutical sciences