Engineering choroid plexus-on-a-chip with oscillatory flow for modeling brain metastasis.

Area of Science:

• Neuroscience and Bioengineering
• Biomimetic Microfluidic Systems

Background:

• The human choroid plexus (ChP) is a vital secretory tissue producing cerebrospinal fluid (CSF) and acting as a blood-CSF barrier.
• Recreating the ChP's complex structure and pulsatile CSF dynamics in a physiologically relevant microenvironment has been a significant challenge.
• Understanding ChP pathophysiology and developing targeted therapies for ChP-related diseases, including brain cancers, requires advanced in vitro models.

Purpose of the Study:

• To develop a microfluidic platform that recapitulates the specialized features and dynamics of the human brain choroid plexus.
• To create a physiologically relevant model for studying ChP function, drug screening, and immune responses within the ChP.
• To investigate cancer cell metastasis and immune cell interactions within the ChP microenvironment.

Main Methods:

• Development of a microfluidic chip designed to mimic ChP structure and CSF flow dynamics.
• Incorporation of a laminin-containing hydrogel to simulate the brain's extracellular matrix (ECM).
• Culture of human ChP cells within the microfluidic device, subjected to simulated in vivo CSF flow and engineered ECM.

Main Results:

• Successful recapitulation of key ChP characteristics, including capillaries, epithelial layers, and secreted components, within the microfluidic environment.
• Demonstration of the device's drug screening capabilities using physiologically relevant responses from breast cancer cells metastasized to the ChP.
• Recapitulation of ChP immune responses, evidenced by macrophage motility and cytotoxic effects, highlighting the model's utility for immunological studies.

Conclusions:

• The developed human ChP-on-a-chip provides a powerful, physiologically relevant microenvironment for studying ChP biology.
• This innovative platform facilitates the elucidation of ChP pathophysiology and supports the development of novel therapeutics for ChP-related diseases.
• The device shows significant potential for advancing research into cancers that have metastasized into the ChP and for understanding neuroimmune interactions.