The HCMEC/D3 Cell Line As a Model of the Human Blood Brain Barrier

Overview

Journal Fluids Barriers CNS

Publisher Biomed Central

Date 2013 Mar 28

PMID 23531482

Citations 310

Authors

Babette Weksler

Ignacio A Romero

Pierre-Olivier Couraud

Affiliations

Soon will be listed here.

Abstract

Since the first attempts in the 1970s to isolate cerebral microvessel endothelial cells (CECs) in order to model the blood-brain barrier (BBB) in vitro, the need for a human BBB model that closely mimics the in vivo phenotype and is reproducible and easy to grow, has been widely recognized by cerebrovascular researchers in both academia and industry. While primary human CECs would ideally be the model of choice, the paucity of available fresh human cerebral tissue makes wide-scale studies impractical. The brain microvascular endothelial cell line hCMEC/D3 represents one such model of the human BBB that can be easily grown and is amenable to cellular and molecular studies on pathological and drug transport mechanisms with relevance to the central nervous system (CNS). Indeed, since the development of this cell line in 2005 over 100 studies on different aspects of cerebral endothelial biology and pharmacology have been published. Here we review the suitability of this cell line as a human BBB model for pathogenic and drug transport studies and we critically consider its advantages and limitations.

Citing Articles

Impact of Tick-Borne Infection on Compact Human Brain Endothelial Barrier.

Schweitzer F, Letoha T, Osterhaus A, Prajeeth C Int J Mol Sci. 2025; 26(5).

PMID: 40076965 PMC: 11901142. DOI: 10.3390/ijms26052342.

Development and Blood-Brain Barrier Penetration of Nanovesicles Loaded with Cannabidiol.

Grifoni L, Landucci E, Pieraccini G, Mazzantini C, Bergonzi M, Pellegrini-Giampietro D Pharmaceuticals (Basel). 2025; 18(2).

PMID: 40005974 PMC: 11859449. DOI: 10.3390/ph18020160.

Comprehensive Physicochemical Characterization and in Vitro Human Cell Culture Studies of an Innovative Biocompatible and Biodegradable Silk-Derived Protein Hydrolysate, SDP-4.

Shafi H, Lora A, Aggarwal S, Infanger D, Lawrence B, Mansour H ACS Omega. 2025; 10(3):2762-2777.

PMID: 39895742 PMC: 11780451. DOI: 10.1021/acsomega.4c08514.

Advances in modeling permeability and selectivity of the blood-brain barrier using microfluidics.

Sun J, Song S Microfluid Nanofluidics. 2025; 28(7.

PMID: 39781566 PMC: 11709447. DOI: 10.1007/s10404-024-02741-z.

Nanostructured lipid carriers for enhanced batimastat delivery across the blood-brain barrier: an in vitro study for glioblastoma treatment.

Horta M, Soares P, Sarmento B, Leite Pereira C, Lima R Drug Deliv Transl Res. 2025; .

PMID: 39760929 DOI: 10.1007/s13346-024-01775-8.

References

Bahbouhi B, Berthelot L, Pettre S, Michel L, Wiertlewski S, Weksler B . Peripheral blood CD4+ T lymphocytes from multiple sclerosis patients are characterized by higher PSGL-1 expression and transmigration capacity across a human blood-brain barrier-derived endothelial cell line. J Leukoc Biol. 2009; 86(5):1049-63. DOI: 10.1189/jlb.1008666. View

Andras I, Eum S, Toborek M . Lipid rafts and functional caveolae regulate HIV-induced amyloid beta accumulation in brain endothelial cells. Biochem Biophys Res Commun. 2012; 421(2):177-83. PMC: 3348457. DOI: 10.1016/j.bbrc.2012.03.128. View

Sano Y, Shimizu F, Abe M, Maeda T, Kashiwamura Y, Ohtsuki S . Establishment of a new conditionally immortalized human brain microvascular endothelial cell line retaining an in vivo blood-brain barrier function. J Cell Physiol. 2010; 225(2):519-28. DOI: 10.1002/jcp.22232. View

Coureuil M, Lecuyer H, Scott M, Boularan C, Enslen H, Soyer M . Meningococcus Hijacks a β2-adrenoceptor/β-Arrestin pathway to cross brain microvasculature endothelium. Cell. 2010; 143(7):1149-60. DOI: 10.1016/j.cell.2010.11.035. View

Hurst L, Bunning R, Couraud P, Romero I, Weksler B, Sharrack B . Expression of ADAM-17, TIMP-3 and fractalkine in the human adult brain endothelial cell line, hCMEC/D3, following pro-inflammatory cytokine treatment. J Neuroimmunol. 2009; 210(1-2):108-12. DOI: 10.1016/j.jneuroim.2009.02.008. View

Hatherell K, Couraud P, Romero I, Weksler B, Pilkington G . Development of a three-dimensional, all-human in vitro model of the blood-brain barrier using mono-, co-, and tri-cultivation Transwell models. J Neurosci Methods. 2011; 199(2):223-9. DOI: 10.1016/j.jneumeth.2011.05.012. View

Andras I, Rha G, Huang W, Eum S, Couraud P, Romero I . Simvastatin protects against amyloid beta and HIV-1 Tat-induced promoter activities of inflammatory genes in brain endothelial cells. Mol Pharmacol. 2008; 73(5):1424-33. PMC: 2731660. DOI: 10.1124/mol.107.042028. View

Liebner S, Corada M, Bangsow T, Babbage J, Taddei A, Czupalla C . Wnt/beta-catenin signaling controls development of the blood-brain barrier. J Cell Biol. 2008; 183(3):409-17. PMC: 2575783. DOI: 10.1083/jcb.200806024. View

Fasler-Kan E, Suenderhauf C, Barteneva N, Poller B, Gygax D, Huwyler J . Cytokine signaling in the human brain capillary endothelial cell line hCMEC/D3. Brain Res. 2010; 1354:15-22. DOI: 10.1016/j.brainres.2010.07.077. View

10.

Mkrtchyan H, Scheler S, Klein I, Fahr A, Couraud P, Romero I . Molecular cytogenetic characterization of the human cerebral microvessel endothelial cell line hCMEC/D3. Cytogenet Genome Res. 2009; 126(4):313-7. DOI: 10.1159/000253080. View

11.

Huang W, Rha G, Chen L, Seelbach M, Zhang B, Andras I . Inhibition of telomerase activity alters tight junction protein expression and induces transendothelial migration of HIV-1-infected cells. Am J Physiol Heart Circ Physiol. 2010; 298(4):H1136-45. PMC: 2853419. DOI: 10.1152/ajpheart.01126.2009. View

12.

Li T, Bourgeois J, Celli S, Glacial F, Le Sourd A, Mecheri S . Cell-penetrating anti-GFAP VHH and corresponding fluorescent fusion protein VHH-GFP spontaneously cross the blood-brain barrier and specifically recognize astrocytes: application to brain imaging. FASEB J. 2012; 26(10):3969-79. DOI: 10.1096/fj.11-201384. View

13.

Wassmer S, Combes V, Candal F, Juhan-Vague I, Grau G . Platelets potentiate brain endothelial alterations induced by Plasmodium falciparum. Infect Immun. 2005; 74(1):645-53. PMC: 1346683. DOI: 10.1128/IAI.74.1.645-653.2006. View

14.

Lecuyer H, Nassif X, Coureuil M . Two strikingly different signaling pathways are induced by meningococcal type IV pili on endothelial and epithelial cells. Infect Immun. 2011; 80(1):175-86. PMC: 3255667. DOI: 10.1128/IAI.05837-11. View

15.

Chaitanya G, Cromer W, Wells S, Jennings M, Couraud P, Romero I . Gliovascular and cytokine interactions modulate brain endothelial barrier in vitro. J Neuroinflammation. 2011; 8:162. PMC: 3248576. DOI: 10.1186/1742-2094-8-162. View

16.

Dickens D, Owen A, Alfirevic A, Giannoudis A, Davies A, Weksler B . Lamotrigine is a substrate for OCT1 in brain endothelial cells. Biochem Pharmacol. 2012; 83(6):805-14. DOI: 10.1016/j.bcp.2011.12.032. View

17.

Kamiichi A, Furihata T, Kishida S, Ohta Y, Saito K, Kawamatsu S . Establishment of a new conditionally immortalized cell line from human brain microvascular endothelial cells: a promising tool for human blood-brain barrier studies. Brain Res. 2012; 1488:113-22. DOI: 10.1016/j.brainres.2012.09.042. View

18.

Prudhomme J, Sherman I, Land K, Moses A, Stenglein S, Nelson J . Studies of Plasmodium falciparum cytoadherence using immortalized human brain capillary endothelial cells. Int J Parasitol. 1996; 26(6):647-55. DOI: 10.1016/0020-7519(96)00027-6. View

19.

Zougbede S, Miller F, Ravassard P, Rebollo A, Ciceron L, Couraud P . Metabolic acidosis induced by Plasmodium falciparum intraerythrocytic stages alters blood-brain barrier integrity. J Cereb Blood Flow Metab. 2010; 31(2):514-26. PMC: 3049507. DOI: 10.1038/jcbfm.2010.121. View

20.

Lopez-Ramirez M, Fischer R, Torres-Badillo C, Davies H, Logan K, Pfizenmaier K . Role of caspases in cytokine-induced barrier breakdown in human brain endothelial cells. J Immunol. 2012; 189(6):3130-9. DOI: 10.4049/jimmunol.1103460. View