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Fluids and Barriers of the CNS
Published in: Fluids and Barriers of the CNS 1/2020

01-12-2020 | Cytokines | Review

In vitro modeling of blood–brain barrier and interface functions in neuroimmune communication

Authors: Michelle A. Erickson, Miranda L. Wilson, William A. Banks

Published in: Fluids and Barriers of the CNS | Issue 1/2020

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Abstract

Neuroimmune communication contributes to both baseline and adaptive physiological functions, as well as disease states. The vascular blood–brain barrier (BBB) and associated cells of the neurovascular unit (NVU) serve as an important interface for immune communication between the brain and periphery through the blood. Immune functions and interactions of the BBB and NVU in this context can be categorized into at least five neuroimmune axes, which include (1) immune modulation of BBB impermeability, (2) immune regulation of BBB transporters, secretions, and other functions, (3) BBB uptake and transport of immunoactive substances, (4) immune cell trafficking, and (5) BBB secretions of immunoactive substances. These axes may act separately or in concert to mediate various aspects of immune signaling at the BBB. Much of what we understand about immune axes has been from work conducted using in vitro BBB models, and recent advances in BBB and NVU modeling highlight the potential of these newer models for improving our understanding of how the brain and immune system communicate. In this review, we discuss how conventional in vitro models of the BBB have improved our understanding of the 5 neuroimmune axes. We further evaluate the existing literature on neuroimmune functions of novel in vitro BBB models, such as those derived from human induced pluripotent stem cells (iPSCs) and discuss their utility in evaluating aspects of neuroimmune communication.
Literature
1.
Erickson MA, Banks WA. Neuroimmune axes of the blood–brain barriers and blood–brain interfaces: bases for physiological regulation, disease states, and pharmacological interventions. Pharmacol Rev. 2018;70(2):278–314.PubMedPubMedCentralCrossRef
2.
Bernas MJ, Cardoso FL, Daley SK, Weinand ME, Campos AR, Ferreira AJ, Hoying JB, Witte MH, Brites D, Persidsky Y, 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(7):1265–72.PubMedPubMedCentralCrossRef
3.
Weksler BB, Subileau EA, Perriere N, Charneau P, Holloway K, Leveque M, Tricoire-Leignel H, Nicotra A, Bourdoulous S, Turowski P, et al. Blood–brain barrier-specific properties of a human adult brain endothelial cell line. FASEB J. 2005;19(13):1872–4.PubMedCrossRef
4.
Lippmann ES, Azarin SM, Kay JE, Nessler RA, Wilson HK, Al-Ahmad A, Palecek SP, Shusta EV. Derivation of blood–brain barrier endothelial cells from human pluripotent stem cells. Nat Biotechnol. 2012;30(8):783–91.PubMedPubMedCentralCrossRef
5.
Sivandzade F, Cucullo L. In-vitro blood–brain barrier modeling: a review of modern and fast-advancing technologies. J Cereb Blood Flow Metab. 2018;38(10):1667–81.PubMedPubMedCentralCrossRef
6.
Pham MT, Pollock KM, Rose MD, Cary WA, Stewart HR, Zhou P, Nolta JA, Waldau B. Generation of human vascularized brain organoids. NeuroReport. 2018;29(7):588–93.PubMedPubMedCentralCrossRef
7.
Cakir B, Xiang Y, Tanaka Y, Kural MH, Parent M, Kang YJ, Chapeton K, Patterson B, Yuan Y, He CS, et al. Engineering of human brain organoids with a functional vascular-like system. Nat Methods. 2019;16(11):1169–75.PubMedCrossRefPubMedCentral
8.
Luissint AC, Artus C, Glacial F, Ganeshamoorthy K, Couraud PO. Tight junctions at the blood brain barrier: physiological architecture and disease-associated dysregulation. Fluids Barriers CNS. 2012;9(1):23.PubMedPubMedCentralCrossRef
9.
Ben-Zvi A, Lacoste B, Kur E, Andreone BJ, Mayshar Y, Yan H, Gu C. Mfsd2a is critical for the formation and function of the blood–brain barrier. Nature. 2014;509(7501):507–11.PubMedPubMedCentralCrossRef
10.
11.
Hartz AM, Bauer B. ABC transporters in the CNS—an inventory. Curr Pharm Biotechnol. 2011;12(4):656–73.PubMedCrossRef
12.
Banks WA. From blood–brain barrier to blood–brain interface: new opportunities for CNS drug delivery. Nat Rev Drug Discov. 2016;15(4):275–92.PubMedCrossRef
13.
Osada T, Gu YH, Kanazawa M, Tsubota Y, Hawkins BT, Spatz M, Milner R, del Zoppo GJ. Interendothelial claudin-5 expression depends on cerebral endothelial cell-matrix adhesion by beta(1)-integrins. J Cereb Blood Flow Metab. 2011;31(10):1972–85.PubMedPubMedCentralCrossRef
14.
McConnell HL, Kersch CN, Woltjer RL, Neuwelt EA. The translational significance of the neurovascular unit. J Biol Chem. 2017;292(3):762–70.PubMedCrossRef
15.
Varatharaj A, Galea I. The blood–brain barrier in systemic inflammation. Brain Behav Immun. 2017;60:1–12.PubMedCrossRef
16.
17.
Abbott NJ, Ronnback L, Hansson E. Astrocyte-endothelial interactions at the blood–brain barrier. Nat Rev Neurosci. 2006;7(1):41–53.PubMedCrossRef
18.
Alvarez JI, Dodelet-Devillers A, Kebir H, Ifergan I, Fabre PJ, Terouz S, Sabbagh M, Wosik K, Bourbonniere L, Bernard M, et al. The Hedgehog pathway promotes blood–brain barrier integrity and CNS immune quiescence. Science. 2011;334(6063):1727–31.PubMedCrossRef
19.
Mathiisen TM, Lehre KP, Danbolt NC, Ottersen OP. The perivascular astroglial sheath provides a complete covering of the brain microvessels: an electron microscopic 3D reconstruction. Glia. 2010;58(9):1094–103.PubMedCrossRef
20.
21.
Dore-Duffy P, Cleary K. Morphology and properties of pericytes. Methods Mol Biol. 2011;686:49–68.PubMedCrossRef
22.
Daneman R, Zhou L, Kebede AA, Barres BA. Pericytes are required for blood–brain barrier integrity during embryogenesis. Nature. 2010;468(7323):562–6.PubMedPubMedCentralCrossRef
23.
Nakagawa S, Deli MA, Nakao S, Honda M, Hayashi K, Nakaoke R, Kataoka Y, Niwa M. Pericytes from brain microvessels strengthen the barrier integrity in primary cultures of rat brain endothelial cells. Cell Mol Neurobiol. 2007;27(6):687–94.PubMedCrossRef
24.
Dohgu S, Takata F, Yamauchi A, Nakagawa S, Egawa T, Naito M, Tsuruo T, Sawada Y, Niwa M, Kataoka Y. Brain pericytes contribute to the induction and up-regulation of blood–brain barrier functions through transforming growth factor-beta production. Brain Res. 2005;1038(2):208–15.PubMedCrossRef
25.
Helms HC, Abbott NJ, Burek M, Cecchelli R, Couraud PO, Deli MA, Forster C, Galla HJ, Romero IA, Shusta EV, 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(5):862–90.PubMedPubMedCentralCrossRef
26.
Andrews AM, Lutton EM, Cannella LA, Reichenbach N, Razmpour R, Seasock MJ, Kaspin SJ, Merkel SF, Langford D, Persidsky Y, et al. Characterization of human fetal brain endothelial cells reveals barrier properties suitable for in vitro modeling of the BBB with syngenic co-cultures. J Cereb Blood Flow Metab. 2018;38(5):888–903.PubMedCrossRef
27.
Persidsky Y, Stins M, Way D, Witte MH, Weinand M, Kim KS, Bock P, Gendelman HE, Fiala M. A model for monocyte migration through the blood–brain barrier during HIV-1 encephalitis. J Immunol. 1997;158(7):3499–510.PubMed
28.
Ramirez SH, Fan S, Dykstra H, Rom S, Mercer A, Reichenbach NL, Gofman L, Persidsky Y. Inhibition of glycogen synthase kinase 3beta promotes tight junction stability in brain endothelial cells by half-life extension of occludin and claudin-5. PLoS ONE. 2013;8(2):e55972.PubMedPubMedCentralCrossRef
29.
Ghosh C, Hossain M, Mishra S, Khan S, Gonzalez-Martinez J, Marchi N, Janigro D, Bingaman W, Najm I. Modulation of glucocorticoid receptor in human epileptic endothelial cells impacts drug biotransformation in an in vitro blood–brain barrier model. Epilepsia. 2018;59(11):2049–60.PubMedPubMedCentralCrossRef
30.
MacLean AG, Orandle MS, MacKey J, Williams KC, Alvarez X, Lackner AA. Characterization of an in vitro rhesus macaque blood–brain barrier. J Neuroimmunol. 2002;131(1–2):98–103.PubMedPubMedCentralCrossRef
31.
Montesano R, Pepper MS, Mohle-Steinlein U, Risau W, Wagner EF, Orci L. Increased proteolytic activity is responsible for the aberrant morphogenetic behavior of endothelial cells expressing the middle T oncogene. Cell. 1990;62(3):435–45.PubMedCrossRef
32.
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(1):41–58.PubMedCrossRef
33.
Gaillard PJ, de Boer AG. Relationship between permeability status of the blood–brain barrier and in vitro permeability coefficient of a drug. Eur J Pharm Sci. 2000;12(2):95–102.PubMedCrossRef
34.
Stamatovic SM, Shakui P, Keep RF, Moore BB, Kunkel SL, Van Rooijen N, Andjelkovic AV. Monocyte chemoattractant protein-1 regulation of blood–brain barrier permeability. J Cereb Blood Flow Metab. 2005;25(5):593–606.PubMedCrossRef
35.
Banks WA, Gray AM, Erickson MA, Salameh TS, Damodarasamy M, Sheibani N, Meabon JS, Wing EE, Morofuji Y, Cook DG, et al. Lipopolysaccharide-induced blood–brain barrier disruption: roles of cyclooxygenase, oxidative stress, neuroinflammation, and elements of the neurovascular unit. J Neuroinflamm. 2015;12:223.CrossRef
36.
Toborek M, Lee YW, Flora G, Pu H, Andras IE, Wylegala E, Hennig B, Nath A. Mechanisms of the blood–brain barrier disruption in HIV-1 infection. Cell Mol Neurobiol. 2005;25(1):181–99.PubMedCrossRef
37.
Leda AR, Bertrand L, Andras IE, El-Hage N, Nair M, Toborek M. Selective disruption of the blood–brain barrier by Zika Virus. Front Microbiol. 2019;10:2158.PubMedPubMedCentralCrossRef
38.
Flierl MA, Stahel PF, Rittirsch D, Huber-Lang M, Niederbichler AD, Hoesel LM, Touban BM, Morgan SJ, Smith WR, Ward PA, et al. Inhibition of complement C5a prevents breakdown of the blood–brain barrier and pituitary dysfunction in experimental sepsis. Crit Care. 2009;13(1):R12.PubMedPubMedCentralCrossRef
39.
Hsuchou H, Kastin AJ, Mishra PK, Pan W. C-reactive protein increases BBB permeability: implications for obesity and neuroinflammation. Cell Physiol Biochem. 2012;30(5):1109–19.PubMedCrossRef
40.
Chow BW, Nunez V, Kaplan L, Granger AJ, Bistrong K, Zucker HL, Kumar P, Sabatini BL, Gu C. Caveolae in CNS arterioles mediate neurovascular coupling. Nature. 2020;579(7797):106–10.PubMedCrossRefPubMedCentral
41.
Srinivasan B, Kolli AR, Esch MB, Abaci HE, Shuler ML, Hickman JJ. TEER measurement techniques for in vitro barrier model systems. J Lab Autom. 2015;20(2):107–26.PubMedPubMedCentralCrossRef
42.
43.
Smith QR, Rapoport SI. Cerebrovascular permeability coefficients to sodium, potassium, and chloride. J Neurochem. 1986;46(6):1732–42.PubMedCrossRef
44.
Lohmann C, Huwel S, Galla HJ. Predicting blood–brain barrier permeability of drugs: evaluation of different in vitro assays. J Drug Target. 2002;10(4):263–76.PubMedCrossRef
45.
Mantle JL, Min L, Lee KH. Minimum transendothelial electrical resistance thresholds for the study of small and large molecule drug transport in a human in vitro blood–brain barrier model. Mol Pharm. 2016;13(12):4191–8.PubMedCrossRef
46.
Hoheisel D, Nitz T, Franke H, Wegener J, Hakvoort A, Tilling T, Galla HJ. Hydrocortisone reinforces the blood–brain barrier properties in a serum free cell culture system. Biochem Biophys Res Commun. 1998;244(1):312–6.PubMedCrossRef
47.
Dehouck MP, Jolliet-Riant P, Bree F, Fruchart JC, Cecchelli R, Tillement JP. Drug transfer across the blood–brain barrier: correlation between in vitro and in vivo models. J Neurochem. 1992;58(5):1790–7.PubMedCrossRef
48.
Harazin A, Bocsik A, Barna L, Kincses A, Varadi J, Fenyvesi F, Tubak V, Deli MA, Vecsernyes M. Protection of cultured brain endothelial cells from cytokine-induced damage by alpha-melanocyte stimulating hormone. PeerJ. 2018;6:e4774.PubMedPubMedCentralCrossRef
49.
Deli MA, Abraham CS, Kataoka Y, Niwa M. Permeability studies on in vitro blood–brain barrier models: physiology, pathology, and pharmacology. Cell Mol Neurobiol. 2005;25(1):59–127.PubMedCrossRef
50.
Descamps L, Coisne C, Dehouck B, Cecchelli R, Torpier G. Protective effect of glial cells against lipopolysaccharide-mediated blood–brain barrier injury. Glia. 2003;42(1):46–58.PubMedCrossRef
51.
Veszelka S, Pasztoi M, Farkas AE, Krizbai I, Ngo TK, Niwa M, Abraham CS, Deli MA. Pentosan polysulfate protects brain endothelial cells against bacterial lipopolysaccharide-induced damages. Neurochem Int. 2007;50(1):219–28.PubMedCrossRef
52.
Wong D, Dorovini-Zis K, Vincent SR. Cytokines, nitric oxide, and cGMP modulate the permeability of an in vitro model of the human blood–brain barrier. Exp Neurol. 2004;190(2):446–55.PubMedCrossRef
53.
Cardoso FL, Kittel A, Veszelka S, Palmela I, Toth A, Brites D, Deli MA, Brito MA. Exposure to lipopolysaccharide and/or unconjugated bilirubin impair the integrity and function of brain microvascular endothelial cells. PLoS ONE. 2012;7(5):e35919.PubMedPubMedCentralCrossRef
54.
Toborek M, Lee YW, Pu H, Malecki A, Flora G, Garrido R, Hennig B, Bauer HC, Nath A. HIV-Tat protein induces oxidative and inflammatory pathways in brain endothelium. J Neurochem. 2003;84(1):169–79.PubMedCrossRef
55.
Kanmogne GD, Primeaux C, Grammas P. HIV-1 gp120 proteins alter tight junction protein expression and brain endothelial cell permeability: implications for the pathogenesis of HIV-associated dementia. J Neuropathol Exp Neurol. 2005;64(6):498–505.PubMedCrossRef
56.
57.
Wang H, Sun J, Goldstein H. Human immunodeficiency virus type 1 infection increases the in vivo capacity of peripheral monocytes to cross the blood–brain barrier into the brain and the in vivo sensitivity of the blood–brain barrier to disruption by lipopolysaccharide. J Virol. 2008;82(15):7591–600.PubMedPubMedCentralCrossRef
58.
de Vries HE, Blom-Roosemalen MC, van Oosten M, de Boer AG, van Berkel TJ, Breimer DD, Kuiper J. The influence of cytokines on the integrity of the blood–brain barrier in vitro. J Neuroimmunol. 1996;64(1):37–43.PubMedCrossRef
59.
Deli MA, Descamps L, Dehouck MP, Cecchelli R, Joo F, Abraham CS, Torpier G. Exposure of tumor necrosis factor-alpha to luminal membrane of bovine brain capillary endothelial cells cocultured with astrocytes induces a delayed increase of permeability and cytoplasmic stress fiber formation of actin. J Neurosci Res. 1995;41(6):717–26.PubMedCrossRef
60.
Megra BW, Eugenin EA, Berman JW. Inflammatory mediators reduce surface PrP(c) on human BMVEC resulting in decreased barrier integrity. Lab Invest. 2018;98(10):1347–59.PubMedPubMedCentralCrossRef
61.
Rom S, Dykstra H, Zuluaga-Ramirez V, Reichenbach NL, Persidsky Y. miR-98 and let-7g* protect the blood–brain barrier under neuroinflammatory conditions. J Cereb Blood Flow Metab. 2015;35(12):1957–65.PubMedPubMedCentralCrossRef
62.
Dimitrijevic OB, Stamatovic SM, Keep RF, Andjelkovic AV. Effects of the chemokine CCL2 on blood–brain barrier permeability during ischemia-reperfusion injury. J Cereb Blood Flow Metab. 2006;26(6):797–810.PubMedCrossRef
63.
Stamatovic SM, Dimitrijevic OB, Keep RF, Andjelkovic AV. Protein kinase Calpha-RhoA cross-talk in CCL2-induced alterations in brain endothelial permeability. J Biol Chem. 2006;281(13):8379–88.PubMedCrossRef
64.
Stamatovic SM, Keep RF, Wang MM, Jankovic I, Andjelkovic AV. Caveolae-mediated internalization of occludin and claudin-5 during CCL2-induced tight junction remodeling in brain endothelial cells. J Biol Chem. 2009;284(28):19053–66.PubMedPubMedCentralCrossRef
65.
Abbott NJ. Inflammatory mediators and modulation of blood–brain barrier permeability. Cell Mol Neurobiol. 2000;20(2):131–47.PubMedCrossRef
66.
Moreira AP, Texeira TF, Ferreira AB, Peluzio Mdo C, Alfenas Rde C. Influence of a high-fat diet on gut microbiota, intestinal permeability and metabolic endotoxaemia. Br J Nutr. 2012;108(5):801–9.PubMedCrossRef
67.
Costa RJS, Snipe RMJ, Kitic CM, Gibson PR. Systematic review: exercise-induced gastrointestinal syndrome-implications for health and intestinal disease. Aliment Pharmacol Ther. 2017;46(3):246–65.PubMedCrossRef
68.
Knowland D, Arac A, Sekiguchi KJ, Hsu M, Lutz SE, Perrino J, Steinberg GK, Barres BA, Nimmerjahn A, Agalliu D. Stepwise recruitment of transcellular and paracellular pathways underlies blood–brain barrier breakdown in stroke. Neuron. 2014;82(3):603–17.PubMedPubMedCentralCrossRef
69.
Lossinsky AS, Shivers RR. Structural pathways for macromolecular and cellular transport across the blood–brain barrier during inflammatory conditions. Review. Histol Histopathol. 2004;19(2):535–64.PubMed
70.
Banks WA. The blood–brain barrier in neuroimmunology: tales of separation and assimilation. Brain Behav Immun. 2015;44:1–8.PubMedCrossRef
71.
Ek M, Engblom D, Saha S, Blomqvist A, Jakobsson PJ, Ericsson-Dahlstrand A. Inflammatory response: pathway across the blood–brain barrier. Nature. 2001;410(6827):430–1.PubMedCrossRef
72.
Garcia-Bueno B, Serrats J, Sawchenko PE. Cerebrovascular cyclooxygenase-1 expression, regulation, and role in hypothalamic-pituitary-adrenal axis activation by inflammatory stimuli. J Neurosci. 2009;29(41):12970–81.PubMedPubMedCentralCrossRef
73.
Risau W, Engelhardt B, Wekerle H. Immune function of the blood–brain barrier: incomplete presentation of protein (auto-)antigens by rat brain microvascular endothelium in vitro. J Cell Biol. 1990;110(5):1757–66.PubMedCrossRef
74.
Banks WA, Dohgu S, Lynch JL, Fleegal-DeMotta MA, Erickson MA, Nakaoke R, Vo TQ. Nitric oxide isoenzymes regulate lipopolysaccharide-enhanced insulin transport across the blood–brain barrier. Endocrinology. 2008;149(4):1514–23.PubMedPubMedCentralCrossRef
75.
Storck SE, Hartz AMS, Bernard J, Wolf A, Kachlmeier A, Mahringer A, Weggen S, Pahnke J, Pietrzik CU. The concerted amyloid-beta clearance of LRP1 and ABCB1/P-gp across the blood–brain barrier is linked by PICALM. Brain Behav Immun. 2018;73:21–33.PubMedCrossRefPubMedCentral
76.
Rhea EM, Rask-Madsen C, Banks WA. Insulin transport across the blood–brain barrier can occur independently of the insulin receptor. J Physiol. 2018;596(19):4753–65.PubMedPubMedCentralCrossRef
77.
Banks WA, Niehoff ML, Martin D, Farrell CL. Leptin transport across the blood–brain barrier of the Koletsky rat is not mediated by a product of the leptin receptor gene. Brain Res. 2002;950(1–2):130–6.PubMedCrossRef
78.
Banks WA. The blood–brain barrier as an endocrine tissue. Nat Rev Endocrinol. 2019;15(8):444–55.PubMedCrossRef
79.
Yu C, Kastin AJ, Tu H, Waters S, Pan W. TNF activates P-glycoprotein in cerebral microvascular endothelial cells. Cell Physiol Biochem. 2007;20(6):853–8.PubMedCrossRef
80.
Hartz AM, Bauer B, Fricker G, Miller DS. Rapid modulation of P-glycoprotein-mediated transport at the blood–brain barrier by tumor necrosis factor-alpha and lipopolysaccharide. Mol Pharmacol. 2006;69(2):462–70.PubMedCrossRef
81.
Matsumoto J, Dohgu S, Takata F, Nishioku T, Sumi N, Machida T, Takahashi H, Yamauchi A, Kataoka Y. Lipopolysaccharide-activated microglia lower P-glycoprotein function in brain microvascular endothelial cells. Neurosci Lett. 2012;524(1):45–8.PubMedCrossRef
82.
Boitsova EB, Morgun AV, Osipova ED, Pozhilenkova EA, Martinova GP, Frolova OV, Olovannikova RY, Tohidpour A, Gorina YV, Panina YA, et al. The inhibitory effect of LPS on the expression of GPR81 lactate receptor in blood–brain barrier model in vitro. J Neuroinflamm. 2018;15(1):196.CrossRef
83.
Dohgu S, Fleegal-DeMotta MA, Banks WA. Lipopolysaccharide-enhanced transcellular transport of HIV-1 across the blood–brain barrier is mediated by luminal microvessel IL-6 and GM-CSF. J Neuroinflamm. 2011;8:167.CrossRef
84.
Dohgu S, Banks WA. Brain pericytes increase the lipopolysaccharide-enhanced transcytosis of HIV-1 free virus across the in vitro blood–brain barrier: evidence for cytokine-mediated pericyte-endothelial cell crosstalk. Fluids Barriers CNS. 2013;10(1):23.PubMedPubMedCentralCrossRef
85.
Calabria AR, Shusta EV. A genomic comparison of in vivo and in vitro brain microvascular endothelial cells. J Cereb Blood Flow Metab. 2008;28(1):135–48.PubMedCrossRef
86.
Banks WA, Kovac A, Morofuji Y. Neurovascular unit crosstalk: pericytes and astrocytes modify cytokine secretion patterns of brain endothelial cells. J Cereb Blood Flow Metab. 2018;38(6):1104–18.PubMedCrossRef
87.
Minten C, Alt C, Gentner M, Frei E, Deutsch U, Lyck R, Schaeren-Wiemers N, Rot A, Engelhardt B. DARC shuttles inflammatory chemokines across the blood–brain barrier during autoimmune central nervous system inflammation. Brain. 2014;137(Pt 5):1454–69.PubMedPubMedCentralCrossRef
88.
Thery C, Ostrowski M, Segura E. Membrane vesicles as conveyors of immune responses. Nat Rev Immunol. 2009;9(8):581–93.PubMedCrossRef
89.
Matsumoto J, Stewart T, Banks WA, Zhang J. The transport mechanism of extracellular vesicles at the blood–brain barrier. Curr Pharm Des. 2017;23(40):6206–14.PubMedCrossRef
90.
Yuan D, Zhao Y, Banks WA, Bullock KM, Haney M, Batrakova E, Kabanov AV. Macrophage exosomes as natural nanocarriers for protein delivery to inflamed brain. Biomaterials. 2017;142:1–12.PubMedPubMedCentralCrossRef
91.
Chen CC, Liu L, Ma F, Wong CW, Guo XE, Chacko JV, Farhoodi HP, Zhang SX, Zimak J, Segaliny A, et al. Elucidation of exosome migration across the blood–brain barrier model in vitro. Cell Mol Bioeng. 2016;9(4):509–29.PubMedCrossRef
92.
Ajikumar A, Long MB, Heath PR, Wharton SB, Ince PG, Ridger VC, Simpson JE. Neutrophil-derived microvesicle induced dysfunction of brain microvascular endothelial cells in vitro. Int J Mol Sci. 2019;20(20):5227.PubMedCentralCrossRef
93.
Filiano AJ, Gadani SP, Kipnis J. How and why do T cells and their derived cytokines affect the injured and healthy brain? Nat Rev Neurosci. 2017;18(6):375–84.PubMedPubMedCentralCrossRef
94.
Banks WA, Niehoff ML, Ponzio NM, Erickson MA, Zalcman SS. Pharmacokinetics and modeling of immune cell trafficking: quantifying differential influences of target tissues versus lymphocytes in SJL and lipopolysaccharide-treated mice. J Neuroinflamm. 2012;9:231.CrossRef
95.
Greenwood J, Heasman SJ, Alvarez JI, Prat A, Lyck R, Engelhardt B. Review: leucocyte-endothelial cell crosstalk at the blood–brain barrier: a prerequisite for successful immune cell entry to the brain. Neuropathol Appl Neurobiol. 2011;37(1):24–39.PubMedCrossRef
96.
Coisne C, Dehouck L, Faveeuw C, Delplace Y, Miller F, Landry C, Morissette C, Fenart L, Cecchelli R, Tremblay P, et al. Mouse syngenic in vitro blood–brain barrier model: a new tool to examine inflammatory events in cerebral endothelium. Lab Invest. 2005;85(6):734–46.PubMedCrossRef
97.
Coisne C, Faveeuw C, Delplace Y, Dehouck L, Miller F, Cecchelli R, Dehouck B. Differential expression of selectins by mouse brain capillary endothelial cells in vitro in response to distinct inflammatory stimuli. Neurosci Lett. 2006;392(3):216–20.PubMedCrossRef
98.
DeStefano JG, Xu ZS, Williams AJ, Yimam N, Searson PC. Effect of shear stress on iPSC-derived human brain microvascular endothelial cells (dhBMECs). Fluids Barriers CNS. 2017;14(1):20.PubMedPubMedCentralCrossRef
99.
Engelhardt B, Coisne C. Fluids and barriers of the CNS establish immune privilege by confining immune surveillance to a two-walled castle moat surrounding the CNS castle. Fluids Barriers CNS. 2011;8(1):4.PubMedPubMedCentralCrossRef
100.
Abadier M, Haghayegh Jahromi N, Cardoso Alves L, Boscacci R, Vestweber D, Barnum S, Deutsch U, Engelhardt B, Lyck R. Cell surface levels of endothelial ICAM-1 influence the transcellular or paracellular T-cell diapedesis across the blood–brain barrier. Eur J Immunol. 2015;45(4):1043–58.PubMedCrossRef
101.
Steiner O, Coisne C, Engelhardt B, Lyck R. Comparison of immortalized bEnd5 and primary mouse brain microvascular endothelial cells as in vitro blood–brain barrier models for the study of T cell extravasation. J Cereb Blood Flow Metab. 2011;31(1):315–27.PubMedCrossRef
102.
Weiss JM, Nath A, Major EO, Berman JW. HIV-1 Tat induces monocyte chemoattractant protein-1-mediated monocyte transmigration across a model of the human blood–brain barrier and up-regulates CCR5 expression on human monocytes. J Immunol. 1999;163(5):2953–9.PubMed
103.
Calderon TM, Williams DW, Lopez L, Eugenin EA, Cheney L, Gaskill PJ, Veenstra M, Anastos K, Morgello S, Berman JW. Dopamine increases CD14(+)CD16(+) monocyte transmigration across the blood brain barrier: implications for substance abuse and HIV neuropathogenesis. J Neuroimmune Pharmacol. 2017;12(2):353–70.PubMedPubMedCentralCrossRef
104.
Persidsky Y, Fan S, Dykstra H, Reichenbach NL, Rom S, Ramirez SH. Activation of cannabinoid type two receptors (CB2) diminish inflammatory responses in macrophages and brain endothelium. J Neuroimmune Pharmacol. 2015;10(2):302–8.PubMedPubMedCentralCrossRef
105.
Lazarevic I, Engelhardt B. Modeling immune functions of the mouse blood-cerebrospinal fluid barrier in vitro: primary rather than immortalized mouse choroid plexus epithelial cells are suited to study immune cell migration across this brain barrier. Fluids Barriers CNS. 2016;13:2.PubMedPubMedCentralCrossRef
106.
Nishihara H, Soldati S, Mossu A, Rosito M, Rudolph H, Muller WA, Latorre D, Sallusto F, Sospedra M, Martin R, et al. Human CD4(+) T cell subsets differ in their abilities to cross endothelial and epithelial brain barriers in vitro. Fluids Barriers CNS. 2020;17(1):3.PubMedPubMedCentralCrossRef
107.
108.
Eugenin EA, Berman JW. Chemokine-dependent mechanisms of leukocyte trafficking across a model of the blood–brain barrier. Methods. 2003;29(4):351–61.PubMedCrossRef
109.
Ramirez SH, Fan S, Zhang M, Papugani A, Reichenbach N, Dykstra H, Mercer AJ, Tuma RF, Persidsky Y. Inhibition of glycogen synthase kinase 3beta (GSK3beta) decreases inflammatory responses in brain endothelial cells. Am J Pathol. 2010;176(2):881–92.PubMedPubMedCentralCrossRef
110.
Paul D, Baena V, Ge S, Jiang X, Jellison ER, Kiprono T, Agalliu D, Pachter JS. Appearance of claudin-5(+) leukocytes in the central nervous system during neuroinflammation: a novel role for endothelial-derived extracellular vesicles. J Neuroinflamm. 2016;13(1):292.CrossRef
111.
Andrews AM, Lutton EM, Merkel SF, Razmpour R, Ramirez SH. Mechanical injury induces brain endothelial-derived microvesicle release: implications for cerebral vascular injury during traumatic brain injury. Front Cell Neurosci. 2016;10:43.PubMedPubMedCentralCrossRef
112.
Lippmann ES, Al-Ahmad A, Azarin SM, Palecek SP, Shusta EV. A retinoic acid-enhanced, multicellular human blood–brain barrier model derived from stem cell sources. Sci Rep. 2014;4:4160.PubMedPubMedCentralCrossRef
113.
Neal EH, Marinelli NA, Shi Y, McClatchey PM, Balotin KM, Gullett DR, Hagerla KA, Bowman AB, Ess KC, Wikswo JP, et al. A simplified, fully defined differentiation scheme for producing blood–brain barrier endothelial cells from human iPSCs. Stem Cell Rep. 2019;12(6):1380–8.CrossRef
114.
Lauschke K, Frederiksen L, Hall VJ. Paving the way toward complex blood–brain barrier models using pluripotent stem cells. Stem Cells Dev. 2017;26(12):857–74.PubMedCrossRef
115.
Canfield SG, Stebbins MJ, Faubion MG, Gastfriend BD, Palecek SP, Shusta EV. An isogenic neurovascular unit model comprised of human induced pluripotent stem cell-derived brain microvascular endothelial cells, pericytes, astrocytes, and neurons. Fluids Barriers CNS. 2019;16(1):25.PubMedPubMedCentralCrossRef
116.
Lim RG, Quan C, Reyes-Ortiz AM, Lutz SE, Kedaigle AJ, Gipson TA, Wu J, Vatine GD, Stocksdale J, Casale MS, et al. Huntington’s disease iPSC-derived brain microvascular endothelial cells reveal WNT-mediated angiogenic and blood–brain barrier deficits. Cell Rep. 2017;19(7):1365–77.PubMedPubMedCentralCrossRef
117.
Vatine GD, Al-Ahmad A, Barriga BK, Svendsen S, Salim A, Garcia L, Garcia VJ, Ho R, Yucer N, Qian T, et al. Modeling psychomotor retardation using iPSCs from MCT8-deficient patients indicates a prominent role for the blood–brain barrier. Cell Stem Cell. 2017;20(6):831–843.e835.PubMedPubMedCentralCrossRef
118.
Patel R, Page S, Al-Ahmad AJ. Isogenic blood–brain barrier models based on patient-derived stem cells display inter-individual differences in cell maturation and functionality. J Neurochem. 2017;142(1):74–88.PubMedCrossRef
119.
Clark PA, Al-Ahmad AJ, Qian T, Zhang RR, Wilson HK, Weichert JP, Palecek SP, Kuo JS, Shusta EV. Analysis of cancer-targeting alkylphosphocholine analogue permeability characteristics using a human induced pluripotent stem cell blood–brain barrier model. Mol Pharm. 2016;13(9):3341–9.PubMedPubMedCentralCrossRef
120.
Appelt-Menzel A, Cubukova A, Gunther K, Edenhofer F, Piontek J, Krause G, Stuber T, Walles H, Neuhaus W, Metzger M. Establishment of a human blood–brain barrier co-culture model mimicking the neurovascular unit using induced pluri- and multipotent stem cells. Stem Cell Rep. 2017;8(4):894–906.CrossRef
121.
Appelt-Menzel A, Cubukova A, Metzger M. Establishment of a human blood–brain barrier co-culture model mimicking the neurovascular unit using induced pluripotent stem cells. Curr Protoc Stem Cell Biol. 2018;47(1):e62.PubMedCrossRef
122.
123.
Bosworth AM, Faley SL, Bellan LM, Lippmann ES. Modeling neurovascular disorders and therapeutic outcomes with human-induced pluripotent stem cells. Front Bioeng Biotechnol. 2017;5:87.PubMedCrossRef
124.
Wilson HK, Canfield SG, Hjortness MK, Palecek SP, Shusta EV. Exploring the effects of cell seeding density on the differentiation of human pluripotent stem cells to brain microvascular endothelial cells. Fluids Barriers CNS. 2015;12:13.PubMedPubMedCentralCrossRef
125.
126.
Qian T, Maguire SE, Canfield SG, Bao X, Olson WR, Shusta EV, Palecek SP. Directed differentiation of human pluripotent stem cells to blood–brain barrier endothelial cells. Sci Adv. 2017;3(11):e1701679.PubMedPubMedCentralCrossRef
127.
Mantle JL, Lee KH. A differentiating neural stem cell-derived astrocytic population mitigates the inflammatory effects of TNF-alpha and IL-6 in an iPSC-based blood–brain barrier model. Neurobiol Dis. 2018;119:113–20.PubMedCrossRef
128.
Linville RM, DeStefano JG, Sklar MB, Xu Z, Farrell AM, Bogorad MI, Chu C, Walczak P, Cheng L, Mahairaki V, et al. Human iPSC-derived blood–brain barrier microvessels: validation of barrier function and endothelial cell behavior. Biomaterials. 2019;190–191:24–37.PubMedCrossRef
129.
Brown JA, Codreanu SG, Shi M, Sherrod SD, Markov DA, Neely MD, Britt CM, Hoilett OS, Reiserer RS, Samson PC, et al. Metabolic consequences of inflammatory disruption of the blood–brain barrier in an organ-on-chip model of the human neurovascular unit. J Neuroinflamm. 2016;13(1):306.CrossRef
130.
Daneman R, Zhou L, Agalliu D, Cahoy JD, Kaushal A, Barres BA. The mouse blood–brain barrier transcriptome: a new resource for understanding the development and function of brain endothelial cells. PLoS ONE. 2010;5(10):e13741.PubMedPubMedCentralCrossRef
131.
Munji RN, Soung AL, Weiner GA, Sohet F, Semple BD, Trivedi A, Gimlin K, Kotoda M, Korai M, Aydin S, et al. Profiling the mouse brain endothelial transcriptome in health and disease models reveals a core blood–brain barrier dysfunction module. Nat Neurosci. 2019;22(11):1892–902.PubMedCrossRefPubMedCentral
132.
Kalari KR, Thompson KJ, Nair AA, Tang X, Bockol MA, Jhawar N, Swaminathan SK, Lowe VJ, Kandimalla KK. BBBomics-human blood brain barrier transcriptomics hub. Front Neurosci. 2016;10:71.PubMedPubMedCentralCrossRef
Metadata
Title
In vitro modeling of blood–brain barrier and interface functions in neuroimmune communication
Authors
Michelle A. Erickson
Miranda L. Wilson
William A. Banks
Publication date
01-12-2020
Publisher
BioMed Central
Keyword
Cytokines
Published in
Fluids and Barriers of the CNS / Issue 1/2020
Electronic ISSN: 2045-8118
DOI
https://doi.org/10.1186/s12987-020-00187-3

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