Host-microbe interactions at the blood-brain barrier through the lens of induced pluripotent stem cell-derived...

Area of Science:

• Neuroscience
• Infectious Diseases
• Stem Cell Biology

Background:

• Meningoencephalitis/meningitis involves pathogens crossing the blood-brain barrier (BBB), a critical interface protecting the central nervous system (CNS).
• The BBB's unique endothelial cells tightly regulate CNS homeostasis, but their specialized nature complicates in vitro modeling.
• Existing models using primary or immortalized brain endothelial cells have limitations in replicating in vivo BBB functions.

Purpose of the Study:

• To review the utility of induced pluripotent stem cell-derived (iPSC-derived) brain-like endothelial cells as an in vitro model for host-pathogen interactions at the BBB.
• To highlight recent advancements and strengths of iPSC-derived endothelial cell models in studying pathogens that breach the BBB.

Main Methods:

• Utilizing iPSC technology to generate brain-like endothelial cells that mimic the human BBB.
• Investigating host-pathogen interactions at the BBB interface in vitro.
• Comparing the iPSC-derived model with traditional in vitro models.

Main Results:

• iPSC-derived brain-like endothelial cells provide a more physiologically relevant in vitro model of the human BBB.
• This model facilitates the study of various pathogens' interactions with the BBB.
• New insights into BBB pathophysiology during infection have been gained that are difficult to achieve with other models.

Conclusions:

• Stem cell-derived brain-like endothelial cells represent a powerful tool for advancing research on CNS infections.
• This advanced in vitro model overcomes limitations of previous cell-based systems for studying BBB integrity and pathogen invasion.