Organoid-engineered neurovascular units for drug discovery and neurodegeneration research

Abstract

The highly selective permeability of the human blood-brain barrier presents a major obstacle to neurological disease modeling. Established 2D cell cultures and animal models are unable to accurately reproduce the physiological and molecular features of the human blood-brain barrier, limiting the translation of bench to bedside. Recent advances in the use of human induced pluripotent stem cells and organoid engineering have enabled the development of more physiologically relevant in vitro brain models for studying blood-brain barrier function. Blood-brain barrier organoids, mimic key structural and functional features of the blood-brain barrier. Moreover, integration of blood brain barrier organoids with brain organoids or microphysiological systems allows the formation of functional neurovascular units that better represent in vivo conditions. The development of scalable, reproducible, and partially vascularized blood-brain barrier organoid models holds promise for high-throughput drug discovery platforms, and the development of personalized therapeutic strategies for central nervous system disorders.

Keywords: Blood–brain barrier (BBB) models, Drug screening, Brain organoids, Human stem cell–derived organoids, Precision medicine, Neurovascular modeling, BBB permeability assays, Translational neuroscience