Blood brain barrier model system: immortalized human brain endothelial cell line
- *Abstract
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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 byINSERM (Stephanie Olas Stephanie.OLAS@inserm-transfert.fr) and is no longer available through Cornell.
The cell line has been licensedto a reagent company where it can be purchased. See: http://www.cellutionsbiosystems.com/index.php?option=com_virtuemart&page=shop.browse&category_id=19&Itemid=35
- *Licensing
- Vibhu Sachdev(212) 746-6187sachdev@cornell.edu
- 其他
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- Afonso PV, et al (2007) Human blood-brain barrier disruption by retroviral-infected lymphocytes: role of myosin light chain kinase in endothelial tight-junction disorganization. J Immunol. 179(4):2576-83.
- Cucullo L, et al (2007) Immortalized human brain endothelial cells and flow-based vascular modeling: a marriage of convenience for rational neurovascular studies. J Cereb Blood Flow Metab. 2007 Jul 4; [Epub ahead of print]
- Schreibelt G, et al (2007) Reactive oxygen species alter brain endothelial tight junction dynamics via RhoA, PI3 kinase, and PKB signaling. FASEB J. 2007 Jun 22; [Epub ahead of print]
- Weksler BB, et al (2005) Blood-brain barrier-specific properties of a human adult brain endothelial cell line. FASEB J. 19(13):1872-4.
- 国家/地区
- 美国
