Paving the Way Toward Complex Blood-Brain Barrier Models Using Pluripotent Stem Cells

Area of Science:

• Neuroscience
• Stem Cell Biology
• Biomedical Engineering

Background:

• The blood-brain barrier (BBB) is crucial for brain homeostasis, protecting the central nervous system from blood-borne substances.
• BBB dysfunction is implicated in various neurological disorders, including Alzheimer's disease, stroke, and multiple sclerosis.
• In vitro models are essential for studying BBB function and pathology due to its complexity.

Purpose of the Study:

• To review recent advancements in using pluripotent stem cells (PSCs) for modeling the blood-brain barrier (BBB) in vitro.
• To explore the potential of patient-specific induced PSCs for modeling BBB dysfunction.
• To identify future directions for improving in vitro BBB models.

Main Methods:

• Review of current literature on PSC differentiation protocols for BBB cell types.
• Analysis of existing in vitro BBB models derived from PSCs.
• Discussion of strategies for enhancing neurovascular unit (NVU) recapitulation in vitro.

Main Results:

• PSCs can be differentiated into various cell types comprising the BBB, enabling partial in vitro recapitulation.
• Patient-specific induced PSCs offer a promising avenue for personalized disease modeling.
• Improvements in pericyte differentiation and NVU modeling are key to advancing in vitro BBB research.

Conclusions:

• Pluripotent stem cell technology has significantly advanced the in vitro modeling of the blood-brain barrier.
• Future research should focus on refining differentiation protocols and enhancing the complexity of in vitro BBB models.
• Improved in vitro BBB models hold promise for understanding disease mechanisms and developing novel therapeutics.