Blood Brain Barrier Model System: Immortalized Human Brain Endothelial Cell Line

Establishment of a human model of the blood-brain barrier has proven to be a difficult goal. To accomplish this, normal human brain endothelial cells were transduced by lentiviral vectors incorporating human telomerase or SV40 T antigen. One was selected for expression of normal endothelial markers, including CD31, VE cadherin, and von Willebrand factor.

This cell line, termed hCMEC/D3:

• has a stable, normal karyotype
• maintained contact-inhibited monolayers in tissue culture
• exhibited robust proliferation in response to endothelial growth factors
• formed capillary tubes in matrix but no colonies in soft agar
• expressed telomerase and grew indefinitely without phenotypic dedifferentiation
• expressed chemokine receptors
• up-regulated adhesion molecules in response to inflammatory cytokines
• demonstrated blood-brain barrier characteristics, including tight junctional proteins and the capacity to actively exclude drugs

hCMEC/D3 are excellent candidates for studies of blood-brain barrier function, the responses of brain endothelium to inflammatory and infectious stimuli, and the interaction of brain endothelium with lymphocytes or tumor cells. Thus, hCMEC/D3 represents the first stable, fully characterized, well-differentiated human brain endothelial cell line and should serve as a widely usable research tool.

Potential Commercial Uses

• Screening drug candidates for ability to cross BBB
• Screening drug candidates for toxicity to BBB

This cell line is managed by INSERM (Stephanie Olas Stephanie.OLAS@inserm-transfert.fr) and is no longer available through Cornell.

The cell line has been licensed to a reagent company where it can be purchased. See here.