A Human Neurovascular Unit On-a-Chip.
Blood–brain barrier
Human induced pluripotent stem cells
Microfluidic
Neurovascular unit
Organotypic model
Journal
Methods in molecular biology (Clifton, N.J.)
ISSN: 1940-6029
Titre abrégé: Methods Mol Biol
Pays: United States
ID NLM: 9214969
Informations de publication
Date de publication:
2022
2022
Historique:
entrez:
14
9
2021
pubmed:
15
9
2021
medline:
6
1
2022
Statut:
ppublish
Résumé
Protection of the central nervous system (CNS) and cerebral homeostasis depend upon the blood-brain barrier (BBB) functions and permeability. BBB restrictive permeability hinders drug delivery for the treatment of several neurodegenerative diseases and brain tumors. Several in vivo animal models and in vitro systems have been developed to understand the BBB complex mechanisms and aid in the design of improved therapeutic strategies. However, there are still many limitations that should be addressed to achieve the structural and chemical environment of a human BBB. We developed a microfluidic-based model of the neurovascular unit. A monolayer of human cerebral endothelial cells (hCMEC-D3) was grown and cocultured with human brain microvascular pericytes (hBMVPC), and human induced pluripotent stem cells differentiated into astrocytes (hiPSC-AC) and neurons (hiPSC-N). To visualize the physiological morphology of each cell type, we used fluorescent cell-specific markers and confocal microscopy. Permeation of fluorescent solutes with different molecular weights was measured to demonstrate that the developed BBB was selectively permeable as a functional barrier.
Identifiants
pubmed: 34520009
doi: 10.1007/978-1-0716-1693-2_7
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
107-119Informations de copyright
© 2022. Springer Science+Business Media, LLC, part of Springer Nature.
Références
Cipolla MJ (2009) Control of cerebral blood flow. Morgan & Claypool Life Sciences, San Rafael
Abbott NJ, Patabendige AAK, Dolman DEM, Yusof SR, Begley DJ (2009) Structure and function of the blood-brain barrier. Neurobiol Dis 37(1):13–25. https://doi.org/10.1016/j.nbd.2009.07.030
doi: 10.1016/j.nbd.2009.07.030
pubmed: 19664713
Feigin VL, Nichols E, Alam T, Bannick MS, Beghi E, Blake N, Culpepper WJ, Dorsey ER, Elbaz A, Ellenbogen RG (2019) Global, regional, and national burden of neurological disorders, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol 18(5):459–480
doi: 10.1016/S1474-4422(18)30499-X
Bell RD, Berislav AE, Zlokovic V (2009) Neurovascular mechanisms and blood-brain barrier disorder in Alzheimer’s disease. Acta Neuropathol 118(1):103–113. https://doi.org/10.1007/s00401-009-0522-3
doi: 10.1007/s00401-009-0522-3
pubmed: 19319544
pmcid: 2853006
Jain RK, Di Tomaso E, Duda DG, Loeffler JS, Sorensen AG, Batchelor TT (2007) Angiogenesis in brain tumours. Nat Rev Neurosci 8(8):610–622. https://doi.org/10.1038/nrn2175
doi: 10.1038/nrn2175
pubmed: 17643088
Pardridge WM (2016) CSF, blood-brain barrier, and brain drug delivery. Expert Opin Drug Deliv 13(7):963–975. https://doi.org/10.1517/17425247.2016.1171315
doi: 10.1517/17425247.2016.1171315
pubmed: 27020469
Saraiva C, Praça C, Ferreira R, Santos T, Ferreira L, Bernardino L (2016) Nanoparticle-mediated brain drug delivery: overcoming blood-brain barrier to treat neurodegenerative diseases. J Control Release 235:34–47. https://doi.org/10.1016/j.jconrel.2016.05.044
doi: 10.1016/j.jconrel.2016.05.044
pubmed: 27208862
Chen D, Love KT, Chen Y, Eltoukhy AA, Kastrup C, Sahay G, Jeon A, Dong Y, Whitehead KA, Anderson DG (2012) Rapid discovery of potent siRNA-containing lipid nanoparticles enabled by controlled microfluidic formulation. J Am Chem Soc 134(16):6948–6951. https://doi.org/10.1021/ja301621z
doi: 10.1021/ja301621z
pubmed: 22475086
Chen H, Tang L, Qin Y, Yin Y, Tang J, Tang W, Sun X, Zhang Z, Liu J, He Q (2010) Lactoferrin-modified procationic liposomes as a novel drug carrier for brain delivery. Eur J Pharm Sci 40(2):94–102. https://doi.org/10.1016/j.ejps.2010.03.007
doi: 10.1016/j.ejps.2010.03.007
pubmed: 20298779
Gan CW, Feng SS (2010) Transferrin-conjugated nanoparticles of poly (lactide)-D-α-tocopheryl polyethylene glycol succinate diblock copolymer for targeted drug delivery across the blood–brain barrier. Biomaterials 31(30):7748–7757. https://doi.org/10.1016/j.biomaterials.2010.06.053
doi: 10.1016/j.biomaterials.2010.06.053
pubmed: 20673685
Niewoehner J, Bohrmann B, Collin L, Urich E, Sade H, Maier P, Rueger P, Stracke JO, Lau W, Tissot AC, Loetscher H, Ghosh A, Freskgård PO (2014) Increased brain penetration and potency of a therapeutic antibody using a monovalent molecular shuttle. Neuron 81(1):49–60. https://doi.org/10.1016/j.neuron.2013.10.061
doi: 10.1016/j.neuron.2013.10.061
pubmed: 24411731
Wang J, Jensen UB, Jensen GV, Shipovskov S, Balakrishnan VS, Otzen D, Pedersen JS, Besenbacher F, Sutherland DS, Nanosciencecenter I (2011) Soft interactions at nanoparticles alter protein function and conformation in a size dependent manner. Nano Lett 11(11):4985–4991. https://doi.org/10.1021/nl202940k
doi: 10.1021/nl202940k
pubmed: 21981115
van Der Helm MW, Van Der Meer AD, Eijkel JCT, van den Berg A, Segerink LI (2016) Microfluidic organ-on-chip technology for blood-brain barrier research. Tissue Barriers 4(1):e1142493. https://doi.org/10.1080/21688370.2016.1142493
doi: 10.1080/21688370.2016.1142493
pubmed: 27141422
pmcid: 4836466
Baker BM, Chen CS (2012) Deconstructing the third dimension: how 3D culture microenvironments alter cellular cues. J Cell Sci 125(Pt 13):3015–3024. https://doi.org/10.1242/jcs.079509
doi: 10.1242/jcs.079509
pubmed: 22797912
pmcid: 3434846
Bissell MJ, Rizki A, Mian IS (2003) Tissue architecture: the ultimate regulator of breast epithelial function. Curr Opin Cell Biol 15(6):753–762. https://doi.org/10.1016/j.ceb.2003.10.016
doi: 10.1016/j.ceb.2003.10.016
pubmed: 14644202
pmcid: 2933200
Pampaloni F, Reynard EG, Stelzer EHK (2007) The third dimension bridges the gap between cell culture and live tissue. Nat Rev Mol Cell Biol 8(10):839–839. https://doi.org/10.1038/nrm2236
doi: 10.1038/nrm2236
pubmed: 17684528
Osaki T, Shin Y, Sivathanu V, Campisi M, Kamm RD (2018) In vitro microfluidic models for neurodegenerative disorders. Adv Healthc Mater 7(2):1700489. https://doi.org/10.1002/adhm.201700489
doi: 10.1002/adhm.201700489
Hajal C, Campisi M, Mattu C, Chiono V, Kamm RD (2018) In vitro models of molecular and nano-particle transport across the blood-brain barrier. Biomicrofluidics 12(4):42213–42213. https://doi.org/10.1063/1.5027118
doi: 10.1063/1.5027118
Nakagawa S, Deli MA, Kawaguchi H, Shimizudani T, Shimono T, Kittel A, Tanaka K, Niwa M (2009) A new blood–brain barrier model using primary rat brain endothelial cells, pericytes and astrocytes. Neurochem Int 54(3–4):253–263. https://doi.org/10.1016/j.neuint.2008.12.002
doi: 10.1016/j.neuint.2008.12.002
pubmed: 19111869
Poller B, Gutmann H, Krähenbühl S, Weksler B, Romero I, Couraud PO, Tuffin G, Drewe J, Huwyler J (2008) The human brain endothelial cell line hCMEC/D3 as a human blood-brain barrier model for drug transport studies. J Neurochem 107(5):1358–1368. https://doi.org/10.1111/j.1471-4159.2008.05730.x
doi: 10.1111/j.1471-4159.2008.05730.x
pubmed: 19013850
Herland A, van der Meer AD, FitzGerald EA, Park T-E, Sleeboom JJF, Ingber DE (2016) Distinct contributions of astrocytes and pericytes to neuroinflammation identified in a 3D human blood-brain barrier on a chip. PLoS One 11(3):e0150360. https://doi.org/10.1371/journal.pone.0150360
doi: 10.1371/journal.pone.0150360
pubmed: 26930059
pmcid: 4773137
Lamartinière Y, Boucau M-C, Dehouck L, Krohn M, Pahnke J, Candela P, Gosselet F, Fenart L (2018) ABCA7 downregulation modifies cellular cholesterol homeostasis and decreases amyloid-β peptide efflux in an in vitro model of the blood-brain barrier. J Alzheimers Dis 64:1195–1211. https://doi.org/10.3233/JAD-170883
doi: 10.3233/JAD-170883
pubmed: 30010117
Sohet F, Daneman R (2013) Genetic mouse models to study blood-brain barrier development and function. Fluids Barriers CNS 10(3). https://doi.org/10.1186/2045-8118-10-3
Aday S, Cecchelli R, Hallier-Vanuxeem D, Dehouck MP, Ferreira L (2016) Stem cell-based human blood-brain barrier models for drug discovery and delivery. Trends Biotechnol 34(5). https://doi.org/10.1016/j.tibtech.2016.01.001
Hartung T (2013) Food for thought look back in anger – what clinical studies tell us about preclinical work. Altex 30(3):275–291. https://doi.org/10.14573/altex.2013.3.275
doi: 10.14573/altex.2013.3.275
pubmed: 23861075
pmcid: 3790571
Pamies D, Hartung T, Hogberg HT (2014) Biological and medical applications of a brain-on-a-chip. Exp Biol Med 239(9):1096–1107. https://doi.org/10.1177/1535370214537738
doi: 10.1177/1535370214537738
Ledford H (2011) Translational research: 4 ways to fix the clinical trial. Nature 477(7366):526–528. https://doi.org/10.1038/477526a
doi: 10.1038/477526a
pubmed: 21956311
Lee SWL, Campisi M, Osaki T, Possenti L, Mattu C, Adriani G, Kamm RD, Chiono V (2020) Modeling nanocarrier transport across a 3D in vitro human blood-brain–barrier microvasculature. Adv Healthc Mater 9(7):e1901486. https://doi.org/10.1002/adhm.201901486
doi: 10.1002/adhm.201901486
pubmed: 32125776
Adriani G, Ma D, Pavesi A, Kamm RD, Goh ELK (2017) A 3D neurovascular microfluidic model consisting of neurons, astrocytes and cerebral endothelial cells as a blood-brain barrier. Lab Chip 17(3):448–459. https://doi.org/10.1039/c6lc00638h
doi: 10.1039/c6lc00638h
pubmed: 28001148
Bang S, Lee S-R, Ko J, Son K, Tahk D, Ahn J, Im C, Li Jeon N (2017) A low permeability microfluidic blood-brain barrier platform with direct contact between perfusable vascular network and astrocytes. Sci Rep 7:8083. https://doi.org/10.1038/s41598-017-07416-0
doi: 10.1038/s41598-017-07416-0
pubmed: 28808270
pmcid: 5556097
Bhise NS, Ribas J, Manoharan V, Zhang YS, Polini A, Massa S, Dokmeci MR, Khademhosseini A (2014) Organ-on-a-chip platforms for studying drug delivery systems. J Control Release 190:82–93. https://doi.org/10.1016/j.jconrel.2014.05.004
doi: 10.1016/j.jconrel.2014.05.004
pubmed: 24818770
pmcid: 4142092
Campisi M, Shin Y, Osaki T, Hajal C, Chiono V, Kamm RD (2018) 3D self-organized microvascular model of the human blood-brain barrier with endothelial cells, pericytes and astrocytes. Biomaterials 180:117–129. https://doi.org/10.1016/j.biomaterials.2018.07.014
doi: 10.1016/j.biomaterials.2018.07.014
pubmed: 30032046
pmcid: 6201194
Brown JA, Pensabene V, Markov DA, Allwardt V, Neely MD, Shi M, Britt CM, Hoilett OS, Yang Q, Brewer BM, Samson PC, McCawley LJ, May JM, Webb DJ, Li D, Bowman AB, Reiserer RS, Wikswo JP (2015) Recreating blood-brain barrier physiology and structure on chip: a novel neurovascular microfluidic bioreactor. Biomicrofluidics 9(5):054124. https://doi.org/10.1063/1.4934713
doi: 10.1063/1.4934713
pubmed: 26576206
pmcid: 4627929
Choi YJ, Chae S, Kim JH, Barald KF, Park JY, Lee SH (2013) Neurotoxic amyloid beta oligomeric assemblies recreated in microfluidic platform with interstitial level of slow flow. Sci Rep 3:1921. https://doi.org/10.1038/srep01921
doi: 10.1038/srep01921
pubmed: 23719665
pmcid: 3667571
Deosarkar SP, Prabhakarpandian B, Wang B, Sheffield JB, Krynska B, Kiani MF (2015) A novel dynamic neonatal blood-brain barrier on a chip. PLoS One 10(11):e0142725. https://doi.org/10.1371/journal.pone.0142725
doi: 10.1371/journal.pone.0142725
pubmed: 26555149
pmcid: 4640840
Partyka PP, Godsey GA, Galie JR, Kosciuk MC, Acharya NK, Nagele RG, Galie PA (2017) Mechanical stress regulates transport in a compliant 3D model of the blood-brain barrier. Biomaterials 115:30–39. https://doi.org/10.1016/j.biomaterials.2016.11.012
doi: 10.1016/j.biomaterials.2016.11.012
pubmed: 27886553
Cucullo L, Hossain M, Puvenna V, Marchi N, Janigro D (2011) The role of shear stress in blood-brain barrier endothelial physiology. BMC Neurosci 12(1):40–40. https://doi.org/10.1186/1471-2202-12-40
doi: 10.1186/1471-2202-12-40
pubmed: 21569296
pmcid: 3103473
Cho H, Hashimoto T, Wong E, Hori Y, Wood LB, Zhao L, Haigis KM, Hyman BT, Irimia D (2013) Microfluidic chemotaxis platform for differentiating the roles of soluble and bound amyloid-β on microglial accumulation. Sci Rep 3:1823. https://doi.org/10.1038/srep01823
doi: 10.1038/srep01823
pubmed: 23665843
pmcid: 3650586
Kothapalli CR, van Veen E, de Valence S, Chung S, Zervantonakis IK, Gertler FB, Kamm RD (2011) A high-throughput microfluidic assay to study neurite response to growth factor gradients. Lab Chip 11(3):497–507. https://doi.org/10.1039/c0lc00240b
doi: 10.1039/c0lc00240b
pubmed: 21107471
Cucullo L, Hossain M, Rapp E, Manders T, Marchi N, Janigro D (2007) Development of a humanized in vitro blood-brain barrier model to screen for brain penetration of antiepileptic drugs. Epilepsia 48(3):505–516. https://doi.org/10.1111/j.1528-1167.2006.00960.x
doi: 10.1111/j.1528-1167.2006.00960.x
pubmed: 17326793
Cucullo L, Marchi N, Hossain M, Janigro D (2011) A dynamic in vitro BBB model for the study of immune cell trafficking into the central nervous system. J Cereb Blood Flow Metab 31(2):767–777. https://doi.org/10.1038/jcbfm.2010.162
doi: 10.1038/jcbfm.2010.162
pubmed: 20842162
Maoz BM, Herland A, Fitzgerald EA, Grevesse T, Vidoudez C, Pacheco AR, Sheehy SP, Park TE, Dauth S, Mannix R, Budnik N, Shores K, Cho A, Nawroth JC, Segrè D, Budnik B, Ingber DE, Parker KK (2018) A linked organ-on-chip model of the human neurovascular unit reveals the metabolic coupling of endothelial and neuronal cells. Nat Biotechnol 36(9):865–877. https://doi.org/10.1038/nbt.4226
doi: 10.1038/nbt.4226
pubmed: 30125269
Freundt EC, Maynard N, Clancy EK, Roy S, Bousset L, Sourigues Y, Covert M, Melki R, Kirkegaard K, Brahic M (2012) Neuron-to-neuron transmission of α-synuclein fibrils through axonal transport. Ann Neurol 72(4):517–524. https://doi.org/10.1002/ana.23747
doi: 10.1002/ana.23747
pubmed: 23109146
pmcid: 3490229
Park J, Koito H, Li J, Han A (2009) Microfluidic compartmentalized co-culture platform for CNS axon myelination research. Biomed Microdevices 11(6):1145–1153. https://doi.org/10.1007/s10544-009-9331-7
doi: 10.1007/s10544-009-9331-7
pubmed: 19554452
pmcid: 2783938
Taylor AM, Blurton-Jones M, Rhee SW, Cribbs DH, Cotman CW, Jeon NL (2005) A microfluidic culture platform for CNS axonal injury, regeneration and transport. Nat Methods 2(8):599–605. https://doi.org/10.1038/nmeth777
doi: 10.1038/nmeth777
pubmed: 16094385
pmcid: 1558906
Chwalek K, Tang-Schomer MD, Omenetto FG, Kaplan DL (2015) In vitro bioengineered model of cortical brain tissue. Nat Protoc 10(9):1362. https://doi.org/10.1038/nprot.2015.091
doi: 10.1038/nprot.2015.091
pubmed: 26270395
pmcid: 4867028
Terrell-Hall TB, Ammer AG, Griffith JIG, Lockman PR (2017) Permeability across a novel microfluidic blood-tumor barrier model. Fluids Barriers CNS 14(1):3. https://doi.org/10.1186/s12987-017-0050-9
doi: 10.1186/s12987-017-0050-9
pubmed: 28114946
pmcid: 5260004
Lee S, Kang B-M, Kim JH, Min J, Kim HS, Ryu H, Park H, Bae S, Oh D, Choi M (2018) Real-time in vivo two-photon imaging study reveals decreased cerebro-vascular volume and increased blood-brain barrier permeability in chronically stressed mice. Sci Rep 8(1):1–14. https://doi.org/10.1038/s41598-018-30875-y
doi: 10.1038/s41598-018-30875-y
Nhan T, Burgess A, Cho EE, Stefanovic B, Lilge L, Hynynen K (2013) Drug delivery to the brain by focused ultrasound induced blood–brain barrier disruption: quantitative evaluation of enhanced permeability of cerebral vasculature using two-photon microscopy. J Control Release 172(1):274–280. https://doi.org/10.1016/j.jconrel.2013.08.029
doi: 10.1016/j.jconrel.2013.08.029
pubmed: 24008151
Shi L, Palacio-Mancheno P, Badami J, Shin DW, Zeng M, Cardoso L, Tu R, Fu BM (2014) Quantification of transient increase of the blood–brain barrier permeability to macromolecules by optimized focused ultrasound combined with microbubbles. Int J Nanomedicine 9:4437. https://doi.org/10.2147/IJN.S68882
doi: 10.2147/IJN.S68882
pubmed: 25258533
pmcid: 4173757
McDonald JC, Duffy DC, Anderson JR, Chiu DT, Wu H, Schueller OJ, Whitesides GM (2000) Fabrication of microfluidic systems in poly(dimethylsiloxane). Electrophoresis 21:27–40. https://doi.org/10.1002/(SICI)1522-2683(20000101)21:1<27::AID-ELPS27>3.0.CO;2-C
doi: 10.1002/(SICI)1522-2683(20000101)21:1<27::AID-ELPS27>3.0.CO;2-C
pubmed: 10634468
Bai J, Adriani G, Dang TM, Tu TY, Penny HXL, Wong SC et al (2015) Contact-dependent carcinoma aggregate dispersion by M2a macrophages via ICAM-1 and β2 integrin interactions. Oncotarget 6(28):25295–25307. https://doi.org/10.18632/oncotarget.4716
doi: 10.18632/oncotarget.4716
pubmed: 26231039
pmcid: 4694832