Blood Brain Barrier Model with HyStem

Publication Title:

3D Brain Angiogenesis Model to Reconstitute Functional Human Blood-Brain Barrier In Vitro

Advanced BioMatrix Products Used: 

HyStem^®  Thiolated Hyaluronic Acid

How the products were used:

Astrocytes and Fibroblasts were embedded within HyStem Hyaluronic Acid hydrogels within a four channel microfluidic platform to recreate the blood brain barrier microenvironment. 

Article Abstract:

Human central nervous system (CNS) vasculature expresses a distinctive barrier phenotype, blood–brain barrier (BBB). Since the BBB contributes to low efficiency in CNS pharmacotherapy by restricting drug transport, development of in vitro human BBB model has been in demand. Here, we present a microfluidic model of CNS angiogenesis having three-dimensional (3D) lumenized vasculature in concert with perivascular cells. We confirm the necessity of the angiogenic tri-culture system (brain endothelium in direct interaction with pericytes and astrocytes) to attain essential phenotypes of BBB vasculature such as minimized vessel diameter and maximized junction expression. In addition, lower vascular permeability is achieved in tri-culture condition compared to mono-culture condition.

Notably, we focus on reconstituting functional efflux transporter system, including p-glycoprotein (p-gp), which is highly responsible for restrictive drug transport. By conducting Calcein-AM efflux assay on our 3D perfusable vasculature after treatment of efflux transporter inhibitors, we confirm the higher efflux property and prominent effect of inhibitors in tri-culture model. Taken together, we design 3D human BBB model with functional barrier properties based on a developmentally-inspired CNS angiogenesis protocol. We expect the model to contribute to a deeper understanding of pathological CNS angiogenesis and the development of effective CNS medications.

Link to the publication: 

https://onlinelibrary.wiley.com/doi/abs/10.1002/bit.27224