iPSCs-Based Neural 3D Systems: A Multidimensional Approach for Disease Modeling and Drug Discovery

Abstract

Induced pluripotent stem cells (iPSCs)-based two-dimensional (2D) protocols have offered invaluable insights into the pathophysiology of neurological diseases. However, these systems are unable to reproduce complex cytoarchitectural features, cell-cell and tissue-tissue interactions like their in vivo counterpart. Three-dimensional (3D)-based culture protocols, though in their infancy, have offered new insights into modeling human diseases. Human neural organoids try to recapitulate the cellular diversity of complex tissues and can be generated from iPSCs to model the pathophysiology of a wide spectrum of pathologies. The engraftment of iPSCs into mice models and the improvement of differentiation protocols towards 3D cultures has enabled the generation of more complex multicellular systems. Consequently, models of neuropsychiatric disorders, infectious diseases, brain cancer and cerebral hypoxic injury can now be investigated from new perspectives. In this review, we consider the advancements made in modeling neuropsychiatric and neurological diseases with iPSC-derived organoids and their potential use to develop new drugs.