Human pluripotent stem cell-based in vitro models that reflect human physiology have the potential to reduce the number of drug failures in clinical trials, and offer a cost effective approach for assessing chemical safety.  Here, human embryonic stem (ES) cell-derived neural progenitor cells, endothelial cells, mesenchymal stem cells, and microglia/macrophage precursors were combined on chemically-defined poly(ethylene glycol) (PEG) hydrogels and cultured in serum-free media to model cellular interactions of the developing brain.  The precursors self-assembled into 3-dimensional (3D) neural constructs with cortically organized neuronal and glial cells, interconnected vascular networks, and ramified microglia. Replicate constructs were highly reproducible by RNA sequencing (Spearmans correlation coefficients,   0.97) and robustly expressed neurogenesis, vasculature development, and microglia genes.  Finally, linear support vector machines were used to construct a predictive model from RNA sequencing data for 240 neural constructs treated with 60 toxic and non-toxic chemicals, which then correctly classified 9/10 blinded compounds. SOURCE: James Thomson Morgridge Institute for Research

Pluto Bioinformatics

GSE63935: Human pluripotent stem cell-derived neural constructs for predictive neurotoxicity screening