Derivation of blood-brain barrier endothelial cells from human pluripotent stem cells
Open accessAbstract
The blood-brain barrier (BBB) is crucial to the health of the brain and is often compromised in neurological disease. Moreover, because of its barrier properties, this endothelial interface restricts uptake of neurotherapeutics. Thus, a renewable source of human BBB endothelium could spur brain research and pharmaceutical development. Here we show that endothelial cells derived from human pluripotent stem cells (hPSCs) acquire BBB properties when co-differentiated with neural cells that provide relevant cues, including those involved in Wnt/β-catenin signaling. The resulting endothelial cells have many BBB attributes, including well-organized tight junctions, appropriate expression of nutrient transporters and polarized efflux transporter activity. Notably, they respond to astrocytes, acquiring substantial barrier properties as measured by transendothelial electrical resistance (1,450 ± 140 Ω cm2), and they possess molecular permeability that correlates well with in vivo rodent blood-brain transfer coefficients.
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The iBMEC model possesses many BBB-relevant properties, including physiologically relevant TEER values and efflux transporter activity, and expresses a comparable set of BBB genes to those expressed in cultured primary human BMECs and BMECs purified from human brain tissue.
“The model possesses many BBB-relevant properties (Lippmann et al., 2012), including physiologically relevant TEER values and efflux transporter activity, and expresses a comparable set of BBB genes (TJ proteins, ATP-binding cassette [ABC], SLC transporters, etc.) to those expressed in cultured primary human BMECs and to BMECs purified from human brain tissue.”
From Modeling Psychomotor Retardation using iPSCs from MCT8-Deficient Patients Indicates a Prominent Role for the Blood-Brain Barrier (2017) · cites this paper as Lippmann et al., 2012
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Experimental — accuracy not yet measurediBMECs did not express OATP1C1.
“However, as previously described (Lippmann et al., 2012), iBMECs did not express OATP1C1”
From Modeling Psychomotor Retardation using iPSCs from MCT8-Deficient Patients Indicates a Prominent Role for the Blood-Brain Barrier (2017) · cites this paper as Lippmann et al., 2012
DITPA had a lower iBMEC permeability than that reported for BBB-impermeant sucrose using the same iBMEC model.
“Moreover, DITPA had a lower iBMEC permeability than that reported for BBB-impermeant sucrose using the same iBMEC model (Lippmann et al., 2012).”
From Modeling Psychomotor Retardation using iPSCs from MCT8-Deficient Patients Indicates a Prominent Role for the Blood-Brain Barrier (2017) · cites this paper as Lippmann et al., 2012
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Conversion of embryonic stem cells into neuroectodermal precursors in adherent monoculture
Ying, Q.-L., Stavridis, M., Griffiths, D., Li, M., & Smith, A. (2003) · Nature Biotechnology · doi:10.1038/nbt780 · Cited by 1,504 · see citing works
A Membrane Receptor for Retinol Binding Protein Mediates Cellular Uptake of Vitamin A
Kawaguchi, R., Yu, J., Honda, J., Hu, J., Whitelegge, J., Ping, P., Wiita, P., Bok, D., & Sun, H. (2007) · Science · doi:10.1126/science.1136244 · Cited by 836 · see citing works
Feeder-independent culture of human embryonic stem cells
Ludwig, T. E., Bergendahl, V., Levenstein, M. E., Yu, J., Probasco, M. D., & Thomson, J. A. (2006) · Nature Methods · doi:10.1038/nmeth902 · Cited by 681 · see citing works
Essential Regulation of CNS Angiogenesis by the Orphan G Protein–Coupled Receptor GPR124
Kuhnert, F., Mancuso, M. R., Shamloo, A., Wang, H.-T., Choksi, V., Florek, M., Su, H., Fruttiger, M., Young, W. L., Heilshorn, S. C., et al. (2010) · Science · doi:10.1126/science.1196554 · Cited by 301 · see citing works
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Research works printed but not linked: 52
- [1]Butt AM Jones HC Abbott NJ Electrical resistance across the blood-brain barrier in anaesthetized rats: a developmental study The Journal of physiology 1990 429 47 62 2277354 PMC1181686
- [2]Pardridge WM Blood-brain barrier drug targeting: the future of brain drug development Molecular interventions 2003 3 90 105 151 14993430
- [3]Weiss N Miller F Cazaubon S Couraud PO The blood-brain barrier in brain homeostasis and neurological diseases Biochimica et biophysica acta 2009 1788 842 857 19061857
- [4]Deli MA Abraham CS Kataoka Y Niwa M Permeability studies on in vitro blood-brain barrier models: physiology, pathology, and pharmacology Cellular and molecular neurobiology 2005 25 59 127 15962509 PMC11529645
- [5]Syvanen S Species differences in blood-brain barrier transport of three positron emission tomography radioligands with emphasis on P-glycoprotein transport Drug metabolism and disposition: the biological fate of chemicals 2009 37 635 643 19047468
- [6]Warren MS 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 19429473
- [7]Cecchelli R Modelling of the blood-brain barrier in drug discovery and development Nat Rev Drug Discov 2007 6 650 661 17667956
- [8]Weksler BB Blood-brain barrier-specific properties of a human adult brain endothelial cell line Faseb J 2005 19 1872 1874 16141364
- [9]Forster C Differential effects of hydrocortisone and TNFalpha on tight junction proteins in an in vitro model of the human blood-brain barrier The Journal of physiology 2008 586 1937 1949 18258663 PMC2375735
- [10]Man S Human brain microvascular endothelial cells and umbilical vein endothelial cells differentially facilitate leukocyte recruitment and utilize chemokines for T cell migration Clinical & developmental immunology 2008 2008 384982 18320011 PMC2248224
- [11]Thomson JA Embryonic stem cell lines derived from human blastocysts Science (New York, N.Y 1998 282 1145 1147 9804556
- [12]Takahashi K Induction of pluripotent stem cells from adult human fibroblasts by defined factors Cell 2007 131 861 872 18035408
- [13]Yu J Induced pluripotent stem cell lines derived from human somatic cells Science (New York, N.Y 2007 318 1917 1920 18029452
- [14]Goldman O A boost of BMP4 accelerates the commitment of human embryonic stem cells to the endothelial lineage Stem cells (Dayton, Ohio) 2009 27 1750 1759 19544443
- [15]James D Expansion and maintenance of human embryonic stem cell-derived endothelial cells by TGFbeta inhibition is Id1 dependent Nature biotechnology 28 161 166 PMC2931334 20081865
- [16]Levenberg S Golub JS Amit M Itskovitz-Eldor J Langer R Endothelial cells derived from human embryonic stem cells Proceedings of the National Academy of Sciences of the United States of America 2002 99 4391 4396 11917100 PMC123658
- [17]Nakahara M High-efficiency production of subculturable vascular endothelial cells from feeder-free human embryonic stem cells without cell-sorting technique Cloning and stem cells 2009 11 509 522 20025522
- [18]Wang L Endothelial and hematopoietic cell fate of human embryonic stem cells originates from primitive endothelium with hemangioblastic properties Immunity 2004 21 31 41 15345218
- [19]Choi KD Hematopoietic and endothelial differentiation of human induced pluripotent stem cells Stem cells (Dayton, Ohio) 2009 27 559 567 PMC2931800 19259936
- [20]Vodyanik MA Bork JA Thomson JA Slukvin II Human embryonic stem cell-derived CD34+ cells: efficient production in the coculture with OP9 stromal cells and analysis of lymphohematopoietic potential Blood 2005 105 617 626 15374881
- [21]Cleaver O Melton DA Endothelial signaling during development Nature medicine 2003 9 661 668 12778164
- [22]Bauer H Ontogenic expression of the erythroid-type glucose transporter (Glut 1) in the telencephalon of the mouse: correlation to the tightening of the blood-brain barrier Brain Res Dev Brain Res 1995 86 317 325 7656423
- [23]Bauer HC Neovascularization and the appearance of morphological characteristics of the blood-brain barrier in the embryonic mouse central nervous system Brain Res Dev Brain Res 1993 75 269 278 8261616
- [24]Daneman R Zhou L Kebede AA Barres BA Pericytes are required for blood-brain barrier integrity during embryogenesis Nature 468 562 566 20944625 PMC3241506
- [25]Stewart PA Hayakawa K Early ultrastructural changes in blood-brain barrier vessels of the rat embryo Brain Res Dev Brain Res 1994 78 25 34 8004771
- [26]Daneman R Wnt/beta-catenin signaling is required for CNS, but not non-CNS, angiogenesis Proceedings of the National Academy of Sciences of the United States of America 2009 106 641 646 19129494 PMC2626756
- [27]Stenman JM Canonical Wnt signaling regulates organ-specific assembly and differentiation of CNS vasculature Science (New York, N.Y 2008 322 1247 1250 19023080
- [29]Kane NM Derivation of endothelial cells from human embryonic stem cells by directed differentiation: analysis of microRNA and angiogenesis in vitro and in vivo Arteriosclerosis, thrombosis, and vascular biology 30 1389 1397 20431067
- [30]Wang ZZ Endothelial cells derived from human embryonic stem cells form durable blood vessels in vivo Nature biotechnology 2007 25 317 318 17322871
- [31]Daneman R The mouse blood-brain barrier transcriptome: a new resource for understanding the development and function of brain endothelial cells PloS one 5 e13741 21060791 PMC2966423
- [32]Calabria AR Weidenfeller C Jones AR de Vries HE Shusta EV Puromycin-purified rat brain microvascular endothelial cell cultures exhibit improved barrier properties in response to glucocorticoid induction Journal of neurochemistry 2006 97 922 933 16573646
- [33]Yu J Human induced pluripotent stem cells free of vector and transgene sequences Science (New York, N.Y 2009 324 797 801 PMC2758053 19325077
- [34]Liebner S Wnt/beta-catenin signaling controls development of the blood-brain barrier The Journal of cell biology 2008 183 409 417 18955553 PMC2575783
- [35]Xu Q Vascular development in the retina and inner ear: control by Norrin and Frizzled-4, a high-affinity ligand-receptor pair Cell 2004 116 883 895 15035989
- [36]Ye X Norrin, frizzled-4, and Lrp5 signaling in endothelial cells controls a genetic program for retinal vascularization Cell 2009 139 285 298 19837032 PMC2779707
- [37]Robitaille J Mutant frizzled-4 disrupts retinal angiogenesis in familial exudative vitreoretinopathy Nature genetics 2002 32 326 330 12172548
- [39]Szeto W Overexpression of the retinoic acid-responsive gene Stra6 in human cancers and its synergistic induction by Wnt-1 and retinoic acid Cancer research 2001 61 4197 4205 11358845
- [40]Shimomura Y APCDD1 is a novel Wnt inhibitor mutated in hereditary hypotrichosis simplex Nature 464 1043 1047 20393562 PMC3046868
- [41]Anderson KD Angiogenic sprouting into neural tissue requires Gpr124, an orphan G protein-coupled receptor Proceedings of the National Academy of Sciences of the United States of America 108 2807 2812 21282641 PMC3041062
- [42]Cullen M GPR124, an orphan G protein-coupled receptor, is required for CNS-specific vascularization and establishment of the blood-brain barrier Proceedings of the National Academy of Sciences of the United States of America 108 5759 5764 21421844 PMC3078373
- [44]Vittet D Embryonic stem cells differentiate in vitro to endothelial cells through successive maturation steps Blood 1996 88 3424 3431 8896407
- [45]Rubin LL A cell culture model of the blood-brain barrier The Journal of cell biology 1991 115 1725 1735 1661734 PMC2289219
- [46]Liebner S Kniesel U Kalbacher H Wolburg H Correlation of tight junction morphology with the expression of tight junction proteins in blood-brain barrier endothelial cells European journal of cell biology 2000 79 707 717 11089919
- [47]Roberts LM Expression of the thyroid hormone transporters monocarboxylate transporter-8 (SLC16A2) and organic ion transporter-14 (SLCO1C1) at the blood-brain barrier Endocrinology 2008 149 6251 6261 18687783
- [48]Uchida Y Quantitative targeted absolute proteomics of human blood-brain barrier transporters and receptors Journal of neurochemistry 117 333 345 21291474
- [49]Perriere N A functional in vitro model of rat blood-brain barrier for molecular analysis of efflux transporters Brain Res 2007 1150 1 13 17434463
- [50]Cohen-Kashi Malina K Cooper I Teichberg VI Closing the gap between the in-vivo and in-vitro blood-brain barrier tightness Brain Res 2009 1284 12 21 19501061
- [52]Weidenfeller C Svendsen CN Shusta EV Differentiating embryonic neural progenitor cells induce blood-brain barrier properties Journal of neurochemistry 2007 101 555 565 17254017 PMC2657050
- [53]de Planell-Saguer M Rodicio MC Mourelatos Z Rapid in situ codetection of noncoding RNAs and proteins in cells and formalin-fixed paraffin-embedded tissue sections without protease treatment Nature protocols 5 1061 1073 20539282
- [54]Huang SM Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling Nature 2009 461 614 620 19759537
- [55]Dravid G Defining the role of Wnt/beta-catenin signaling in the survival, proliferation, and self-renewal of human embryonic stem cells Stem cells (Dayton, Ohio) 2005 23 1489 1501 16002782
- [56]Tuomi JM Voorbraak F Jones DL Ruijter JM Bias in the Cq value observed with hydrolysis probe based quantitative PCR can be corrected with the estimated PCR efficiency value Methods (San Diego, Calif 50 313 322 20138998
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- Authors
- Lippmann, E. S., Azarin, S. M., Kay, J. E., Nessler, R. A., Wilson, H. K., Al-Ahmad, A., Palecek, S. P., & Shusta, E. V.
- Affiliations
- University of Wisconsin–Madison (US)
- University of Iowa (US)
- Corresponding author
- Palecek, Sean P
- Shusta, Eric V
- Venue
- Nature Biotechnology
- Published
- 2012-06-24
- Volume
- 30
- Issue
- 8
- Pages
- 783-791
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- PMC
- PMC3467331
- OpenAlex
- W2001726213
- Cited by
- 800
- References
- 4
- Citations by year
- 2026: 45 · 2025: 60 · 2024: 83 · 2023: 76 · 2022: 90 · 2021: 73 · 2020: 73 · 2019: 57 · 2018: 57 · 2017: 52 · 2016: 42 · 2015: 30 · 2014: 33 · 2013: 24 · 2012: 4
- FWCI
- 14.66
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (AA020476, RC4AA020476)
- National Cancer Institute (P30CA014520)
- National Institute of General Medical Sciences (T32GM008505)
- National Institute of Neurological Disorders and Stroke (NS056249)
- National Institute of Biomedical Imaging and Bioengineering (EB007534, R01EB007534)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- blood-brain barrier, endothelial cells, human pluripotent stem cells, stem cell differentiation, Wnt/β-catenin signaling, tight junctions, efflux pumps, astrocyte-endothelial interactions, transendothelial electrical resistance, blood-brain barrier permeability, drug screening, neurotherapeutics
- MeSH terms
- Blood-Brain Barrier, Cell Differentiation, Cell Line, Cell Separation, Endothelium, Vascular, Humans, Neurons, Phenotype, Signal Transduction, Coculture Techniques, Pluripotent Stem Cells, Endothelial Cells, Wnt Proteins, beta Catenin
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