3D Bioprinting of Stem Cell-Derived Central Nervous System Cells Enables Astrocyte Growth, Vasculogenesis and Enhances Neural Differentiation/Function

Abstract

Current research tools for pre-clinical drug development such as rodent models and 2D immortalised monocultures have failed to serve as effective translational models for human CNS disorders. Recent advancements in the development of iPSCs and 3D culturing can improve the in vivo-relevance of pre-clinical models, while generating 3D cultures though novel bioprinting technologies can offer increased scalability and replicability. As such, there is a need to develop platforms that combine iPSC-derived cells with 3D bioprinting to produce scalable, tunable and biomimetic cultures for preclinical drug discovery applications. We report a biocompatible PEG-based matrix which incorporates RGD and YIGSR peptide motifs and full length collagen IV at a stiffness similar to the human brain (1.5 kPa). Using a high-throughput commercial bioprinter we report the viable culture and morphological development of iPSC-derived astrocytes, brain microvascular endothelial cells, neural progenitors and neurons in our novel matrix. We also show that this system supports endothelial vasculogenesis and enhances neural differentiation and spontaneous activity. This platform forms a foundation for more complex, multicellular models to facilitate high-throughput translational drug discovery for CNS disorders.