New experimental models of the blood-brain barrier for CNS drug discovery

References

• Huber JD, Egleton RD, Davis TP. Molecular physiology and pathophysiology of tight junctions in the blood-brain barrier. Trends Neurosci. 2001;24:719–725.
   PubMed Web of Science ®Google Scholar
• Huber JD, Witt KA, Hom S, et al. Inflammatory pain alters blood-brain barrier permeability and tight junctional protein expression. Am J Physiol Heart Circ Physiol. 2001;280:H1241–H1248.
   PubMed Web of Science ®Google Scholar
• Tilling T, Engelbertz C, Decker S, et al. Expression and adhesive properties of basement membrane proteins in cerebral capillary endothelial cell cultures. Cell Tissue Res. 2002;310:19–29. DOI:10.1007/s00441-002-0604-1
   PubMed Web of Science ®Google Scholar
• Rosenberg GA, Kornfeld M, Estrada E, et al. TIMP-2 reduces proteolytic opening of blood-brain barrier by type IV collagenase. Brain Res. 1992;576:203–207.
   PubMed Web of Science ®Google Scholar
• Liberto CM, Albrecht PJ, Herx LM, et al. Pro-regenerative properties of cytokine-activated astrocytes. J Neurochem. 2004;89:1092–1100. DOI:10.1111/j.1471-4159.2004.02420.x
   PubMed Web of Science ®Google Scholar
• Alavijeh MS, Chishty M, Qaiser MZ, et al. Drug metabolism and pharmacokinetics, the blood-brain barrier, and central nervous system drug discovery. NeuroRx. 2005;2:554–571. DOI:10.1602/neurorx.2.4.554
   PubMedGoogle Scholar
• Nakagawa S, Deli MA, Nakao S, et al. Pericytes from brain microvessels strengthen the barrier integrity in primary cultures of rat brain endothelial cells. Cell Mol Neurobiol. 2007;27:687–694. DOI:10.1007/s10571-007-9195-4
   PubMed Web of Science ®Google Scholar
• Wang J, Sun L, Si YF, et al. Overexpression of actin-depolymerizing factor blocks oxidized low-density lipoprotein-induced mouse brain microvascular endothelial cell barrier dysfunction. Mol Cell Biochem. 2012;371:1–8. DOI:10.1007/s11010-012-1415-7
   PubMed Web of Science ®Google Scholar
• Shayan G, Choi YS, Shusta EV, et al. Murine in vitro model of the blood-brain barrier for evaluating drug transport. Eur J Pharm Sci. 2011;42:148–155. DOI:10.1016/j.ejps.2010.11.005
   PubMed Web of Science ®Google Scholar
• Daneman R, Zhou L, Kebede AA, et al. Pericytes are required for blood-brain barrier integrity during embryogenesis. Nature. 2010;468:562–566. DOI:10.1038/nature09513
   PubMed Web of Science ®Google Scholar
• Thomsen LB, Burkhart A, Moos T, et al. Model of the blood-brain barrier using porcine brain endothelial cells, astrocytes and pericytes. PLoS One. 2015;10:e0134765. DOI:10.1371/journal.pone.0134765
   Google Scholar
• Xue Q, Liu Y, Qi H, et al. A novel brain neurovascular unit model with neurons, astrocytes and microvascular endothelial cells of rat. Int J Biol Sci. 2013;9:174–189. DOI:10.7150/ijbs.5115
   PubMed Web of Science ®Google Scholar
• Vandenhaute E, Dehouck L, Boucau MC, et al. Modelling the neurovascular unit and the blood-brain barrier with the unique function of pericytes. Curr Neurovasc Res. 2011;8:258–269.
   PubMed Web of Science ®Google Scholar
• Lippmann ES, Weidenfeller C, Svendsen CN, et al. Blood-brain barrier modeling with co-cultured neural progenitor cell-derived astrocytes and neurons. J Neurochem. 2011;119:507–520. DOI:10.1111/j.1471-4159.2011.07434.x
   PubMed Web of Science ®Google Scholar
• Augustine C, Cepinskas G, Fraser DD, et al. Traumatic injury elicits JNK-mediated human astrocyte retraction in vitro. Neuroscience. 2014;274:1–10. DOI:10.1016/j.neuroscience.2014.05.009
   PubMed Web of Science ®Google Scholar
• Cucullo L, Hossain M, Puvenna V, et al. The role of shear stress in Blood-Brain Barrier endothelial physiology. BMC Neurosci. 2011;12:40. DOI:10.1186/1471-2202-12-40
   PubMed Web of Science ®Google Scholar
• Adkins CE, Nounou MI, Mittapalli RK, et al. A novel preclinical method to quantitatively evaluate early-stage metastatic events at the murine blood-brain barrier. Cancer Prev Res (Phila). 2015;8:68–76. DOI:10.1158/1940-6207.CAPR-14-0225
   PubMed Web of Science ®Google Scholar
• Abbott NJ, Patabendige AA, Dolman DE, et al. Structure and function of the blood-brain barrier. Neurobiol Dis. 2010;37:13–25. DOI:10.1016/j.nbd.2009.07.030
   PubMed Web of Science ®Google Scholar
• Stamatovic SM, Keep RF, Kunkel SL, et al. Potential role of MCP-1 in endothelial cell tight junction ‘opening’: signaling via Rho and Rho kinase. J Cell Sci. 2003;116:4615–4628. DOI:10.1242/jcs.00755
   PubMed Web of Science ®Google Scholar
• Perriere N, Demeuse P, Garcia E, et al. Puromycin-based purification of rat brain capillary endothelial cell cultures. Effect on the expression of blood-brain barrier-specific properties. J Neurochem. 2005;93:279–289. DOI:10.1111/j.1471-4159.2004.03020.x
   PubMed Web of Science ®Google Scholar
• Abbott NJ, Dolman DE, Drndarski S, et al. An improved in vitro blood-brain barrier model: rat brain endothelial cells co-cultured with astrocytes. Methods Mol Biol. 2012;814:415–430. DOI:10.1007/978-1-61779-452-0_28
   PubMedGoogle Scholar
• Nakagawa S, Deli MA, Kawaguchi H, et al. A new blood-brain barrier model using primary rat brain endothelial cells, pericytes and astrocytes. Neurochem Int. 2009;54:253–263. DOI:10.1016/j.neuint.2008.12.002
   PubMed Web of Science ®Google Scholar
• Helms HC, Brodin B. Generation of primary cultures of bovine brain endothelial cells and setup of cocultures with rat astrocytes. Methods Mol Biol. 2014;1135:365–382. DOI:10.1007/978-1-4939-0320-7_30
   PubMedGoogle Scholar
• Patabendige A, Skinner RA, Morgan L, et al. A detailed method for preparation of a functional and flexible blood-brain barrier model using porcine brain endothelial cells. Brain Res. 2013;1521:16–30. DOI:10.1016/j.brainres.2013.04.006
   PubMed Web of Science ®Google Scholar
• Rahman NA, Rasil AN, Meyding-Lamade U, et al. Immortalized endothelial cell lines for in vitro blood-brain barrier models: a systematic review. Brain Res. 2016;1642:532–545. DOI:10.1016/j.brainres.2016.04.024
   PubMed Web of Science ®Google Scholar
• Weksler B, Romero IA, Couraud PO. The hCMEC/D3 cell line as a model of the human blood brain barrier. Fluids Barriers CNS. 2013;10:16. DOI:10.1186/2045-8118-10-16
   PubMedGoogle Scholar
• Hatherell K, Couraud PO, Romero IA, et al. 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;199:223–229. DOI:10.1016/j.jneumeth.2011.05.012
   PubMed Web of Science ®Google Scholar
• Watanabe T, Dohgu S, Takata F, et al. Paracellular barrier and tight junction protein expression in the immortalized brain endothelial cell lines bEND.3, bEND.5 and mouse brain endothelial cell 4. Biol Pharm Bull. 2013;36:492–495.
   PubMed Web of Science ®Google Scholar
• Brown RC, Morris AP, O’Neil RG. Tight junction protein expression and barrier properties of immortalized mouse brain microvessel endothelial cells. Brain Res. 2007;1130:17–30. DOI:10.1016/j.brainres.2006.10.083
   PubMed Web of Science ®Google Scholar
• Roux F, Couraud PO. Rat brain endothelial cell lines for the study of blood-brain barrier permeability and transport functions. Cell Mol Neurobiol. 2005;25:41–58.
   PubMed Web of Science ®Google Scholar
• Chiu JJ, Chien S. Effects of disturbed flow on vascular endothelium: pathophysiological basis and clinical perspectives. Physiol Rev. 2011;91:327–387. DOI:10.1152/physrev.00047.2009
   PubMed Web of Science ®Google Scholar
• Colgan OC, Ferguson G, Collins NT, et al. Regulation of bovine brain microvascular endothelial tight junction assembly and barrier function by laminar shear stress. Am J Physiol Heart Circ Physiol. 2007;292:H3190–H3197. DOI:10.1152/ajpheart.01177.2006
   PubMed Web of Science ®Google Scholar
• Wong AD, Ye M, Levy AF, et al. The blood-brain barrier: an engineering perspective. Front Neuroeng. 2013;6:7. DOI:10.3389/fneng.2013.00007
   PubMedGoogle Scholar
• Krizanac-Bengez L, Mayberg MR, Janigro D. The cerebral vasculature as a therapeutic target for neurological disorders and the role of shear stress in vascular homeostatis and pathophysiology. Neurol Res. 2004;26:846–853. DOI:10.1179/016164104X3789
   PubMed Web of Science ®Google Scholar
• Bai K, Wang W. Shear stress-induced redistribution of the glycocalyx on endothelial cells in vitro. Biomech Model Mechanobiol. 2014;13:303–311. DOI:10.1007/s10237-013-0502-3
   PubMed Web of Science ®Google Scholar
• Balaguru UM, Sundaresan L, Manivannan J, et al. Disturbed flow mediated modulation of shear forces on endothelial plane: a proposed model for studying endothelium around atherosclerotic plaques. Sci Rep. 2016;6:27304. DOI:10.1038/srep27304
   PubMed Web of Science ®Google Scholar
• De La Torre JC, Mussivand T. Can disturbed brain microcirculation cause Alzheimer’s disease? Neurol Res. 1993;15:146–153.
   PubMed Web of Science ®Google Scholar
• Desai SY, Marroni M, Cucullo L, et al. Mechanisms of endothelial survival under shear stress. Endothelium. 2002;9:89–102.
   PubMed Web of Science ®Google Scholar
• Stanness KA, Westrum LE, Fornaciari E, et al. Morphological and functional characterization of an in vitro blood-brain barrier model. Brain Res. 1997;771:329–342.
   PubMed Web of Science ®Google Scholar
• Cerutti C, Soblechero-Martin P, Wu D, et al. MicroRNA-155 contributes to shear-resistant leukocyte adhesion to human brain endothelium in vitro. Fluids Barriers CNS. 2016;13:8. DOI:10.1186/s12987-016-0042-1
   PubMedGoogle Scholar
• Cucullo L, Hossain M, Tierney W, et al. A new dynamic in vitro modular capillaries-venules modular system: cerebrovascular physiology in a box. BMC Neurosci. 2013;14:18. DOI:10.1186/1471-2202-14-18
   PubMed Web of Science ®Google Scholar
• Cucullo L, Marchi N, Hossain M, et al. A dynamic in vitro BBB model for the study of immune cell trafficking into the central nervous system. J Cereb Blood Flow Metab. 2011;31:767–777. DOI:10.1038/jcbfm.2010.162
   PubMed Web of Science ®Google Scholar
• Sumpio BJ, Chitragari G, Moriguchi T, et al. African trypanosome-induced blood-brain barrier dysfunction under shear stress may not require ERK activation. Int J Angiol. 2015;24:41–46. DOI:10.1055/s-0034-1370890
   PubMed Web of Science ®Google Scholar
• Cucullo L, Couraud PO, Weksler B, et al. Immortalized human brain endothelial cells and flow-based vascular modeling: a marriage of convenience for rational neurovascular studies. J Cereb Blood Flow Metab. 2008;28:312–328. DOI:10.1038/sj.jcbfm.9600525
   PubMed Web of Science ®Google Scholar
• Siddharthan V, Kim YV, Liu S, et al. Human astrocytes/astrocyte-conditioned medium and shear stress enhance the barrier properties of human brain microvascular endothelial cells. Brain Res. 2007;1147:39–50. DOI:10.1016/j.brainres.2007.02.029
   PubMed Web of Science ®Google Scholar
• Chang E, O’Donnell ME, Barakat AI. Shear stress and 17beta-estradiol modulate cerebral microvascular endothelial Na-K-Cl cotransporter and Na/H exchanger protein levels. Am J Physiol Cell Physiol. 2008;294:C363–C371. DOI:10.1152/ajpcell.00045.2007
   Google Scholar
• Xue S, Wang J, Zhang X, et al. Endothelial ATP-binding cassette G1 in mouse endothelium protects against hemodynamic-induced atherosclerosis. Biochem Biophys Res Commun. 2016;477:247–254. DOI:10.1016/j.bbrc.2016.06.050
   PubMed Web of Science ®Google Scholar
• Palmiotti CA, Prasad S, Naik P, et al. In vitro cerebrovascular modeling in the 21st century: current and prospective technologies. Pharm Res. 2014;31:3229–3250. DOI:10.1007/s11095-014-1464-6
   PubMed Web of Science ®Google Scholar
• Wolff A, Antfolk M, Brodin B, et al. In vitro blood-brain barrier models-an overview of established models and new microfluidic approaches. J Pharm Sci. 2015;104:2727–2746. Epub 2015/01/30. DOI:10.1002/jps.24329
   PubMed Web of Science ®Google Scholar
• McDonald JC, Duffy DC, Anderson JR, et al. Fabrication of microfluidic systems in poly(dimethylsiloxane). Electrophoresis. 2000;21:27–40. Epub 2000/01/14. DOI:10.1002/(SICI)1522-2683(20000101)21:1<27::AID-ELPS27>3.0.CO;2-C
   PubMed Web of Science ®Google Scholar
• Beebe DJ, Mensing GA, Walker GM. Physics and applications of microfluidics in biology. Annu Rev Biomed Eng. 2002;4:261–286. Epub 2002/07/16. DOI:10.1146/annurev.bioeng.4.112601.125916
   PubMed Web of Science ®Google Scholar
• Squires TM, Quake SR. Microfluidics: fluid physics at the nanoliter scale. Rev Mod Phys. 2005;77:977–1026. DOI:10.1103/RevModPhys.77.977
   Web of Science ®Google Scholar
• Ferrell N, Desai RR, Fleischman AJ, et al. A microfluidic bioreactor with integrated transepithelial electrical resistance (TEER) measurement electrodes for evaluation of renal epithelial cells. Biotechnol Bioeng. 2010;107:707–716. Epub 2010/06/17. DOI:10.1002/bit.22835
   PubMed Web of Science ®Google Scholar
• Young EW, Watson MW, Srigunapalan S, et al. Technique for real-time measurements of endothelial permeability in a microfluidic membrane chip using laser-induced fluorescence detection. Anal Chem. 2010;82:808–816. DOI:10.1021/ac901560w
   PubMed Web of Science ®Google Scholar
• Weibel DB, Diluzio WR, Whitesides GM. Microfabrication meets microbiology. Nat Rev Microbiol. 2007;5:209–218. Epub 2007/02/17. DOI:10.1038/nrmicro1616
   PubMed Web of Science ®Google Scholar
• Esch MB, Sung JH, Yang J, et al. On chip porous polymer membranes for integration of gastrointestinal tract epithelium with microfluidic ‘body-on-a-chip’ devices. Biomed Microdevices. 2012;14:895–906. DOI:10.1007/s10544-012-9669-0
   PubMed Web of Science ®Google Scholar
• Esch EW, Bahinski A, Huh D. Organs-on-chips at the frontiers of drug discovery. Nat Rev Drug Discov. 2015;14:248–260. DOI:10.1038/nrd4539
   PubMed Web of Science ®Google Scholar
• Ghaemmaghami AM, Hancock MJ, Harrington H, et al. Biomimetic tissues on a chip for drug discovery. Drug Discov Today. 2012;17:173–181. Epub 2011/11/19. DOI:10.1016/j.drudis.2011.10.029
   PubMed Web of Science ®Google Scholar
• Booth R, Kim H. Characterization of a microfluidic in vitro model of the blood-brain barrier (muBBB). Lab Chip. 2012;12:1784–1792. Epub 2012/03/17. DOI:10.1039/c2lc40094d
   PubMed Web of Science ®Google Scholar
• Griep LM, Wolbers F, De Wagenaar B, et al. BBB on chip: microfluidic platform to mechanically and biochemically modulate blood-brain barrier function. Biomed Microdevices. 2013;15:145–150. Epub 2012/09/08. DOI:10.1007/s10544-012-9699-7
   PubMed Web of Science ®Google Scholar
• Prabhakarpandian B, Shen MC, Nichols JB, et al. SyM-BBB: a microfluidic blood brain barrier model. Lab Chip. 2013;13:1093–1101. Epub 2013/01/25. DOI:10.1039/c2lc41208j
   PubMed Web of Science ®Google Scholar
• Booth R, Kim H. Permeability analysis of neuroactive drugs through a dynamic microfluidic in vitro blood-brain barrier model. Ann Biomed Eng. 2014;42:2379–2391. Epub 2014/08/15. DOI:10.1007/s10439-014-1086-5
   PubMed Web of Science ®Google Scholar
• Srinivasan B, Kolli AR, Esch MB, et al. TEER measurement techniques for in vitro barrier model systems. J Lab Autom. 2015;20:107–126. Epub 2015/01/15. DOI:10.1177/2211068214561025
   PubMedGoogle Scholar
• Brown JA, Pensabene V, Markov DA, et al. Recreating blood-brain barrier physiology and structure on chip: a novel neurovascular microfluidic bioreactor. Biomicrofluidics. 2015;9:054124. Epub 2015/11/18. DOI:10.1063/1.4934713
   PubMed Web of Science ®Google Scholar
• Herland A, van der Meer AD, FitzGerald EA, et al. Distinct contributions of astrocytes and pericytes to neuroinflammation identified in a 3D human blood-brain barrier on a chip. PLoS One. 2016;11:e0150360. Epub 2016/03/02. DOI:10.1371/journal.pone.0150360
   PubMed Web of Science ®Google Scholar
• Bischel LL, Lee SH, Beebe DJ. A practical method for patterning lumens through ECM hydrogels via viscous finger patterning. J Lab Autom. 2012;17:96–103. Epub 2012/02/24. DOI:10.1177/2211068211426694
   PubMedGoogle Scholar
• Edmondson R, Broglie JJ, Adcock AF, et al. Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors. Assay Drug Dev Technol. 2014;12:207–218. DOI:10.1089/adt.2014.573
   PubMed Web of Science ®Google Scholar
• Tibbitt MW, Anseth KS. Hydrogels as extracellular matrix mimics for 3D cell culture. Biotechnol Bioeng. 2009;103:655–663. DOI:10.1002/bit.22361
   PubMed Web of Science ®Google Scholar
• Lee J, Cuddihy MJ, Kotov NA. Three-dimensional cell culture matrices: state of the art. Tissue Eng Part B Rev. 2008;14:61–86. DOI:10.1089/teb.2007.0150
   PubMed Web of Science ®Google Scholar
• Chrobak KM, Potter DR, Tien J. Formation of perfused, functional microvascular tubes in vitro. Microvasc Res. 2006;71:185–196. DOI:10.1016/j.mvr.2006.02.005
   PubMed Web of Science ®Google Scholar
• Tourovskaia A, Fauver M, Kramer G, et al. Tissue-engineered microenvironment systems for modeling human vasculature. Exp Biol Med (Maywood). 2014;239:1264–1271. DOI:10.1177/1535370214539228
   PubMed Web of Science ®Google Scholar
• Munson JM, Bellamkonda RV, Swartz MA. Interstitial flow in a 3D microenvironment increases glioma invasion by a CXCR4-dependent mechanism. Cancer Res. 2013;73:1536–1546. DOI:10.1158/0008-5472.CAN-12-2838
   PubMed Web of Science ®Google Scholar
• Zheng Y, Chen J, Craven M, et al. In vitro microvessels for the study of angiogenesis and thrombosis. Proc Natl Acad Sci U S A. 2012;109:9342–9347. DOI:10.1073/pnas.1201240109
   PubMed Web of Science ®Google Scholar
• Cho H, Seo JH, Wong KH, et al. Three-dimensional blood-brain barrier model for in vitro studies of neurovascular pathology. Sci Rep. 2015;5:15222. DOI:10.1038/srep15222
   PubMed Web of Science ®Google Scholar
• Antoine EE, Vlachos PP, Rylander MN. Review of collagen I hydrogels for bioengineered tissue microenvironments: characterization of mechanics, structure, and transport. Tissue Eng Part B Rev. 2014;20:683–696. DOI:10.1089/ten.TEB.2014.0086
   PubMed Web of Science ®Google Scholar
• Li W, Zhu B, Strakova Z, et al. Two-way regulation between cells and aligned collagen fibrils: local 3D matrix formation and accelerated neural differentiation of human decidua parietalis placental stem cells. Biochem Biophys Res Commun. 2014;450:1377–1382. DOI:10.1016/j.bbrc.2014.06.136
   PubMed Web of Science ®Google Scholar
• Even-Ram S, Yamada KM. Cell migration in 3D matrix. Curr Opin Cell Biol. 2005;17:524–532. DOI:10.1016/j.ceb.2005.08.015
   PubMed Web of Science ®Google Scholar
• Toh YC, Lim TC, Tai D, et al. A microfluidic 3D hepatocyte chip for drug toxicity testing. Lab Chip. 2009;9:2026–2035. DOI:10.1039/b900912d
   PubMed Web of Science ®Google Scholar
• Zervantonakis IK, Hughes-Alford SK, Charest JL, et al. Three-dimensional microfluidic model for tumor cell intravasation and endothelial barrier function. Proc Natl Acad Sci U S A. 2012;109:13515–13520. DOI:10.1073/pnas.1210182109
   PubMed Web of Science ®Google Scholar
• Benton G, Arnaoutova I, George J, et al. Matrigel: from discovery and ECM mimicry to assays and models for cancer research. Adv Drug Deliv Rev. 2014;79-80:3–18. DOI:10.1016/j.addr.2014.06.005
   PubMed Web of Science ®Google Scholar
• Doyle AD, Yamada KM. Mechanosensing via cell-matrix adhesions in 3D microenvironments. Exp Cell Res. 2016;343:60–66. DOI:10.1016/j.yexcr.2015.10.033
   PubMed Web of Science ®Google Scholar
• Shafiee A, Atala A. Printing technologies for medical applications. Trends Mol Med. 2016;22:254–265. DOI:10.1016/j.molmed.2016.01.003
   PubMed Web of Science ®Google Scholar
• Lee VK, Kim DY, Ngo H, et al. Creating perfused functional vascular channels using 3D bio-printing technology. Biomaterials. 2014;35:8092–8102. DOI:10.1016/j.biomaterials.2014.05.083
   PubMed Web of Science ®Google Scholar
• Aday S, Cecchelli R, Hallier-Vanuxeem D, et al. Stem cell-based human blood-brain barrier models for drug discovery and delivery. Trends Biotechnol. 2016;34:382–393. DOI:10.1016/j.tibtech.2016.01.001
   PubMed Web of Science ®Google Scholar
• Shawahna R, Decleves X, Scherrmann JM. Hurdles with using in vitro models to predict human blood-brain barrier drug permeability: a special focus on transporters and metabolizing enzymes. Curr Drug Metab. 2013;14:120–136
   PubMed Web of Science ®Google Scholar
• Syvanen S, Lindhe O, Palner M, et al. Species differences in blood-brain barrier transport of three positron emission tomography radioligands with emphasis on P-glycoprotein transport. Drug Metab Dispos. 2009;37:635–643. DOI:10.1124/dmd.108.024745
   PubMed Web of Science ®Google Scholar
• Warren MS, Zerangue N, Woodford K, et al. Comparative gene expression profiles of ABC transporters in brain microvessel endothelial cells and brain in five species including human. Pharmacol Res. 2009;59:404–413. DOI:10.1016/j.phrs.2009.02.007
   PubMed Web of Science ®Google Scholar
• Wilhelm I, Krizbai IA. In vitro models of the blood-brain barrier for the study of drug delivery to the brain. Mol Pharm. 2014;11:1949–1963. DOI:10.1021/mp500046f
   PubMed Web of Science ®Google Scholar
• Bernas MJ, Cardoso FL, Daley SK, et al. Establishment of primary cultures of human brain microvascular endothelial cells to provide an in vitro cellular model of the blood-brain barrier. Nat Protoc. 2010;5:1265–1272. DOI:10.1038/nprot.2010.76
   PubMed Web of Science ®Google Scholar
• Cayrol R, Haqqani AS, Ifergan I, et al. Isolation of human brain endothelial cells and characterization of lipid raft-associated proteins by mass spectroscopy. Methods Mol Biol. 2011;686:275–295. DOI:10.1007/978-1-60761-938-3_13
   PubMedGoogle Scholar
• Navone SE, Marfia G, Invernici G, et al. Isolation and expansion of human and mouse brain microvascular endothelial cells. Nat Protoc. 2013;8:1680–1693. DOI:10.1038/nprot.2013.107
   PubMed Web of Science ®Google Scholar
• Artus C, Glacial F, Ganeshamoorthy K, et al. The Wnt/planar cell polarity signaling pathway contributes to the integrity of tight junctions in brain endothelial cells. J Cereb Blood Flow Metab. 2014;34:433–440. DOI:10.1038/jcbfm.2013.213
   PubMed Web of Science ®Google Scholar
• Eigenmann DE, Xue G, Kim KS, et al. Comparative study of four immortalized human brain capillary endothelial cell lines, hCMEC/D3, hBMEC, TY10, and BB19, and optimization of culture conditions, for an in vitro blood-brain barrier model for drug permeability studies. Fluids Barriers CNS. 2013;10:33. DOI:10.1186/2045-8118-10-33
   PubMedGoogle Scholar
• Forster C, Burek M, Romero IA, et al. Differential effects of hydrocortisone and TNFalpha on tight junction proteins in an in vitro model of the human blood-brain barrier. J Physiol. 2008;586:1937–1949. DOI:10.1113/jphysiol.2007.146852
   PubMed Web of Science ®Google Scholar
• Strazza M, Maubert ME, Pirrone V, et al. Co-culture model consisting of human brain microvascular endothelial and peripheral blood mononuclear cells. J Neurosci Methods. 2016;269:39–45. DOI:10.1016/j.jneumeth.2016.05.016
   PubMed Web of Science ®Google Scholar
• Weksler BB, Subileau EA, Perriere N, et al. Blood-brain barrier-specific properties of a human adult brain endothelial cell line. Faseb J. 2005;19:1872–1874. DOI:10.1096/fj.04-3458fje
   PubMed Web of Science ®Google Scholar
• Ohtsuki S, Ikeda C, Uchida Y, et al. Quantitative targeted absolute proteomic analysis of transporters, receptors and junction proteins for validation of human cerebral microvascular endothelial cell line hCMEC/D3 as a human blood-brain barrier model. Mol Pharm. 2013;10:289–296. DOI:10.1021/mp3004308
   PubMed Web of Science ®Google Scholar
• Sajja RK, Green KN, Altered Nrf2 CL. signaling mediates hypoglycemia-induced blood-brain barrier endothelial dysfunction in vitro. PLoS One. 2015;10:e0122358. DOI:10.1371/journal.pone.0122358
   Web of Science ®Google Scholar
• Urich E, Lazic SE, Molnos J, et al. Transcriptional profiling of human brain endothelial cells reveals key properties crucial for predictive in vitro blood-brain barrier models. PLoS One. 2012;7:e38149. DOI:10.1371/journal.pone.0038149
   PubMedGoogle Scholar
• Bayzigitov DR, Medvedev SP, Dementyeva EV, et al. Human induced pluripotent stem cell-derived cardiomyocytes afford new opportunities in inherited cardiovascular disease modeling. Cardiol Res Pract. 2016;2016:3582380.
   PubMedGoogle Scholar
• De Vos J, Bouckenheimer J, Sansac C, et al. Human induced pluripotent stem cells: a disruptive innovation. Curr Res Transl Med. 2016;64:91–96. DOI:10.1016/j.retram.2016.04.001
   PubMedGoogle Scholar
• Kramer N, Rosner M, Kovacic B, et al. Full biological characterization of human pluripotent stem cells will open the door to translational research. Arch Toxicol. 2016;90:2173–2186. DOI:10.1007/s00204-016-1763-2
   PubMed Web of Science ®Google Scholar
• Russo FB, Cugola FR, Fernandes IR, et al. Induced pluripotent stem cells for modeling neurological disorders. World J Transplant. 2015;5:209–221. DOI:10.5500/wjt.v5.i4.209
   PubMedGoogle Scholar
• Siddiqi F, Wolfe JH. Stem cell therapy for the central nervous system in lysosomal storage diseases. Hum Gene Ther. 2016;27:749–757. DOI:10.1089/hum.2016.088
   PubMed Web of Science ®Google Scholar
• Gomez-Lechon MJ, Tolosa L. Human hepatocytes derived from pluripotent stem cells: a promising cell model for drug hepatotoxicity screening. Arch Toxicol. 2016;90:2049–2061. DOI:10.1007/s00204-016-1756-1
   PubMed Web of Science ®Google Scholar
• Kawser Hossain M, Abdal Dayem A, Han J, et al. Recent advances in disease modeling and drug discovery for diabetes mellitus using induced pluripotent stem cells. Int J Mol Sci. 2016;17:256. DOI:10.3390/ijms17020256
   PubMed Web of Science ®Google Scholar
• Kelava I, Lancaster MA. Dishing out mini-brains: current progress and future prospects in brain organoid research. Dev Biol. 2016. DOI:10.1016/j.ydbio.2016.06.037
   PubMedGoogle Scholar
• Schmidt BZ, Lehmann M, Gutbier S, et al. In vitro acute and developmental neurotoxicity screening: an overview of cellular platforms and high-throughput technical possibilities. Arch Toxicol. 2016. DOI:10.1007/s00204-016-1805-9
   Google Scholar
• Schutgens F, Verhaar MC, Rookmaaker MB. Pluripotent stem cell-derived kidney organoids: an in vivo-like in vitro technology. Eur J Pharmacol. 2016;790:12–20. DOI:10.1016/j.ejphar.2016.06.059
   PubMed Web of Science ®Google Scholar
• Helms HC, Abbott NJ, Burek M, et al. In vitro models of the blood-brain barrier: an overview of commonly used brain endothelial cell culture models and guidelines for their use. J Cereb Blood Flow Metab. 2016;36:862–890. DOI:10.1177/0271678X16630991
   PubMed Web of Science ®Google Scholar
• Stebbins MJ, Wilson HK, Canfield SG, et al. Differentiation and characterization of human pluripotent stem cell-derived brain microvascular endothelial cells. Methods. 2016;101:93–102. DOI:10.1016/j.ymeth.2015.10.016
   PubMed Web of Science ®Google Scholar
• Boyer-Di Ponio J, El-Ayoubi F, Glacial F, et al. Instruction of circulating endothelial progenitors in vitro towards specialized blood-brain barrier and arterial phenotypes. PLoS One. 2014;9:e84179. DOI:10.1371/journal.pone.0084179
   PubMed Web of Science ®Google Scholar
• Cecchelli R, Aday S, Sevin E, et al. A stable and reproducible human blood-brain barrier model derived from hematopoietic stem cells. PLoS One. 2014;9:e99733. DOI:10.1371/journal.pone.0099733
   PubMed Web of Science ®Google Scholar
• Drolez A, Vandenhaute E, Julien S, et al. Selection of a relevant in vitro blood-brain barrier model to investigate pro-metastatic features of human breast cancer cell lines. PLoS One. 2016;11:e0151155. DOI:10.1371/journal.pone.0151155
   Google Scholar
• Vandenhaute E, Drolez A, Sevin E, et al. Adapting coculture in vitro models of the blood-brain barrier for use in cancer research: maintaining an appropriate endothelial monolayer for the assessment of transendothelial migration. Lab Invest. 2016;96:588–598. DOI:10.1038/labinvest.2016.35
   PubMed Web of Science ®Google Scholar
• Naik P, Cucullo L. In vitro blood-brain barrier models: current and perspective technologies. J Pharm Sci. 2012;101:1337–1354. DOI:10.1002/jps.23022
   PubMed Web of Science ®Google Scholar
• Wilhelm I, Fazakas C, Krizbai IA. In vitro models of the blood-brain barrier. Acta Neurobiol Exp (Wars). 2011;71:113–128.
   PubMed Web of Science ®Google Scholar
• Weidenfeller C, Svendsen CN, Shusta EV. Differentiating embryonic neural progenitor cells induce blood-brain barrier properties. J Neurochem. 2007;101:555–565. DOI:10.1111/j.1471-4159.2006.04394.x
   PubMed Web of Science ®Google Scholar
• Lippmann ES, Al-Ahmad A, Azarin SM, et al. A retinoic acid-enhanced, multicellular human blood-brain barrier model derived from stem cell sources. Sci Rep. 2014;4:4160. DOI:10.1038/srep04160
   PubMed Web of Science ®Google Scholar
• Patel R, Alahmad AJ. Growth-factor reduced Matrigel source influences stem cell derived brain microvascular endothelial cell barrier properties. Fluids Barriers CNS. 2016;13:6. DOI:10.1186/s12987-016-0042-1
   PubMedGoogle Scholar
• Wang YI, Abaci HE, Shuler ML. Microfluidic blood-brain barrier model provides in vivo-like barrier properties for drug permeability screening. Biotechnol Bioeng. 2016. DOI:10.1002/bit.26045
   Google Scholar
• Lippmann ES, Azarin SM, Kay JE, et al. Derivation of blood-brain barrier endothelial cells from human pluripotent stem cells. Nat Biotechnol. 2012;30:783–791. DOI:10.1038/nbt.2247
   PubMed Web of Science ®Google Scholar
• Chou CH, Sinden JD, Couraud PO, et al. In vitro modeling of the neurovascular environment by coculturing adult human brain endothelial cells with human neural stem cells. PLoS One. 2014;9:e106346. DOI:10.1371/journal.pone.0106346
   Google Scholar
• Daneman R, Agalliu D, Zhou L, et al. Wnt/beta-catenin signaling is required for CNS, but not non-CNS, angiogenesis. Proc Natl Acad Sci U S A. 2009;106:641–646. DOI:10.1073/pnas.0805165106
   PubMed Web of Science ®Google Scholar
• Clark PA, Al-Ahmad AJ, Qian T, et al. Analysis of cancer-targeting alkylphosphocholine analogue permeability characteristics using a human induced pluripotent stem cell blood-brain barrier model. Mol Pharm. 2016;13:3341–3349. DOI:10.1021/acs.molpharmaceut.6b00441
   PubMed Web of Science ®Google Scholar
• Abaci HE, Gledhill K, Guo Z, et al. Pumpless microfluidic platform for drug testing on human skin equivalents. Lab Chip. 2015;15:882–888. Epub 2014/12/11. DOI:10.1039/c4lc00999a
   PubMed Web of Science ®Google Scholar
• Loskill P, Marcus SG, Mathur A, et al. muOrgano: a lego(R)-like plug & play system for modular multi-organ-chips. PLoS One. 2015;10:e0139587. Epub 2015/10/07. DOI:10.1371/journal.pone.0139587
   Google Scholar
• Abhyankar VV, Wu M, Koh CY, et al. A reversibly sealed, easy access, modular (SEAM) microfluidic architecture to establish in vitro tissue interfaces. PLoS One. 2016;11:e0156341. Epub 2016/05/27. DOI:10.1371/journal.pone.0156341
   Google Scholar
• Shin JA, Oh S, Ahn JH, et al. Estrogen receptor-mediated resveratrol actions on blood-brain barrier of ovariectomized mice. Neurobiol Aging. 2015;36:993–1006.
   PubMed Web of Science ®Google Scholar
• Paolinelli R, Corada M, Ferrarini L, et al. Wnt activation of immortalized brain endothelial cells as a tool for generating a standardized model of the blood brain barrier in vitro. PLoS One. 2013;8:e70233.
   PubMed Web of Science ®Google Scholar
• Kleinschnitz C, Blecharz K, Kahles T, et al. Glucocorticoid insensitivity at the hypoxic blood-brain barrier can be reversed by inhibition of the proteasome. Stroke. 2011;42:1081–1089.
   PubMed Web of Science ®Google Scholar
• Faria A, Pestana D, Teixeira D, et al. Flavonoid transport across RBE4 cells: A blood-brain barrier model. Cell Mol Biol Lett. 2010;15:234–241.
   PubMed Web of Science ®Google Scholar
• De Bock M, Culot M, Wang N, et al. Low extracellular Ca2+ conditions induce an increase in brain endothelial permeability that involves intercellular Ca2+ waves. Brain Res. 2012;1487:78–87.
   PubMed Web of Science ®Google Scholar
• Prasad S, Sajja RK, Park JH, et al. Impact of cigarette smoke extract and hyperglycemic conditions on blood-brain barrier endothelial cells. Fluids Barriers CNS. 2015;12:18.
   PubMedGoogle Scholar