Work

Advances in hiPSC-Based Models of Complex Neurological Disorders

Year: 2026
Type: book-chapter
Abstract: Human iPSCs (hiPSCs) have revolutionized drug discovery in both academic and biopharmaceutical settings. While new protocols have been developed to generate an abundant supply of diverse cell types, including many in the central nervous system (CNS), efforts to further the maturation and physiological relevance of iPSC-derived cells continue to be important, particularly when modeling aging-related diseases. Despite the successful use of brain organoids in the study of neurodevelopmental disorders, current models have several important limitations. Organoids lack structures observed in the larger in vivo brain, such as cortical layers, thalamic nuclei, the neurovascular unit comprising the blood–brain barrier (BBB), and specific commissures. The dysregulation of these structures, or of communication between them, is involved in the onset of many neurological disorders. Consequently, novel approaches are needed to increase the anatomical relevance of brain organoids. Rapid progress in the field of iPSC-based modeling of neurodevelopmental and neurological disorders has been enabled by advancements in protocols for generating nearly all brain cell types; in methods for further maturing iPSC-derived cells so that they more closely approach their in vivo counterparts; in innovative disease models that encapsulate highly heterogeneous patient populations; in strategies for artificially “aging” cells in vitro; and in methods for generating highly reproducible 3D brain organoid culture systems. The future will likely see mainstream adoption of many of these cutting-edge techniques.
Language: English
Open Access status: hybrid
OpenAlex ID: W7211890620
FWCI:
Cites: 74
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Related to: 10