Human iPSC-Derived Blood-Brain Barrier Models: Valuable Tools for Preclinical Drug Discovery and Development?

Area of Science:

• Neuroscience
• Stem Cell Biology
• Drug Discovery

Background:

• Translating biological knowledge into treatments for CNS disorders is challenging.
• Efficient drug delivery across the blood-brain barrier (BBB) remains a significant hurdle in CNS drug development.

Purpose of the Study:

• To review the potential of human-induced pluripotent stem cell (hiPSC)-derived blood-brain barrier (BBB) models.
• To compare these models with existing in vitro and in vivo models for CNS drug discovery.

Main Methods:

• Review of mono- or co-culture BBB models using hiPSC-derived brain capillary endothelial cells (BCECs).
• Comparison with primary cell-based BBB models, rodent in vivo models, and established barrier models (Caco-2, PAMPA).

Main Results:

• hiPSC-derived BBB models show potential for in vitro testing of drug candidates.
• Discussion of model features, predictivity, and impact on CNS therapeutic development.

Conclusions:

• hiPSC-derived BBB models could significantly impact the discovery and development of novel CNS-targeting therapeutics.
• These models offer a valuable tool for early-stage drug candidate testing, potentially improving efficiency in CNS drug discovery.