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Instructions BBMVEC
5 Important Cell Culture Rules
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Description

Bovine Brain Microvascular Endothelial Cells (BBMVEC) provide an excellent model system to study many aspects of endothelial function and disease, especially those related to the blood-brain barrier (BBB).
 
BBMVEC from Cell Applications, Inc. have been utilized extensively in research, for example to:
  • Show that alkalosis activates ERK in aortic, but not brain microvascular endothelial cells
  • Study the mechanisms of blood-brain barrier (BBB) penetration by fungal pathogens during invasion
  • Demonstrate opposite effects of osteoponin isoforms on angiogenesisin
  • Develop an in vitro capillary assay and show VEGF secretion by endothelial cells
  • Investigate the mechanisms of accumulation and effects of amyloid deposits on brain vasculature in cerebral amyloid angiopathy
  • Improve drug loading and delivery stealth dendrimer carriers
  • Report that the BBB breaks down under hypoxic conditions
  • In indicate that increased contractility and oxidative stress are involved in development of post-stroke brain edema
  • Exhibit blood-brain barrier (BBB) function can result from shear stress, acting through a pathway that upregulates key factors and increases their localization to tight junctions
  • Demonstrate that brain microvascular endothelial cells show higher sensitivity to oxidative stress generated by advanced glycation end products due to stronger VEGF expression leading to increased permeability
  • Show, along with Bovine Aortic Endothelial Cells, that brain microvasculature is more sensitive to pathogenesis, compared to large vessel endothelia,
  • Demonstrate that C-reactive protein (CRP), a cardiovascular risk factor, induces higher oxidative stress in the brain microvasculature
  • Support the key role of ROS by showing that activation of antioxidant genes by Nrf2 reduces brain vascular leak from acute high altitude exposure known to induce ROS
  • Determine that IL-1β, ZYM, and LTA increase the permeability of the BBB to small ions, while TNF-α and lipopolysaccharide disrupt the endothelial layer integrity to allow passage of larger molecules
  • Investigate the role of basolateral environment in modulating BBB by regulating expression and biochemical properties of the tight junction proteins, occludin and ZO-1
  • Show that during cerebral ischemia increased expression of TWEAK and Fn14 in the endothelial-astrocyte interface facilitating leukocyte transmigration and recruitment to the ischemic tissue
  • Demonstrate that apigenin, a dietary flavonoid,  activates Ca2+-activated K+ channels in endothelial cells leading to a hyperpolarization followed by a Ca2+ influx causing increased NO production followed by Akt dephosphorylation
  • Develop gene and drug delivery methods for crossing the BBB based on polymer-based nanoparticles or adenovirus or gold nanoparticles modified to be transported via transcytosis pathway
(Click to Enlarge) Bovine Brain Microvascular Endothelial Cells: BBMVEC.  Isolated from small cerebral blood vessels.

Details

Tissue
Normal healthy bovine brain microvessels
QC
No bacteria, yeast, fungi, mycoplasma
Character
DiI-Ac-LDL uptake: Positive
Bioassay
Attach, spread on Attachment Factor-coated surface, proliferate in Growth Med
Cryovial
500,000 BBMVEC (2nd passage) frozen in Basal Medium w/ 10% FBS, 10% DMSO
Kit
Cryovial frozen BBMVEC (B840-05), Gr Med (B819-500), Attchmnt Fctr Soln (123-100), Subcltr Rgnt Kit (090K)
Proliferating
Shipped in Gr Med, 3rd psg (flasks or plates)
Doublings
At least 12
Applications
Laboratory research use only (RUO). Not for human, clinical, diagnostic or veterinary use.
Instructions BBMVEC

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Products

Product Size CAT.# Price Quantity
Cryopreserved BBMVEC: Frozen BBMVEC (5x10^5) Size: 1 Cryovial CAT.#: B840-05 Price: $758.76
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Cryopreserved BBMVEC Total Kit: 5x10^5 Cells, Medium & Subculture Reagents (See Details tab for specifics) Size: 1 Kit CAT.#: B840K-05 Price: $922.37
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Proliferating BBMVEC: Actively growing, dividing cells in medium Size: T-25 Flask CAT.#: B841-25 Price: $758.76
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Proliferating BBMVEC: Actively growing, dividing cells in medium Size: T-75 Flask CAT.#: B841-75 Price: $930.96
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Proliferating BBMVEC: Actively growing, dividing cells in medium Size: 6 Well CAT.#: B841-6W Price: $930.96
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Proliferating BBMVEC: Actively growing, dividing cells in medium Size: 96 Well CAT.#: B841-96W Price: $1,060.11
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Related Products

Product Size CAT.# Price Quantity
Bovine Brain Endothelial Cell Basal Medium: Basal medium (contains no growth supplement).  Add GS before use. Size: 500 ml CAT.#: B818-500 Price: $57.04
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Bovine Brain Endothelial Cell Growth Medium: All-in-one ready-to-use Size: 500 ml CAT.#: B819-500 Price: $105.47
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Bovine Brain Endothelial Cell Growth Medium Kit: Basal medium & growth supplement sold together packaged separately Size: Yields 500 ml CAT.#: B819K-500 Price: $113.01
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Bovine Brain Endothelial Cell Growth Supplement: Added to Basal Medium to create Growth Medium Size: 50 ml x 2 CAT.#: B819-GS Price: $57.04
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Extended Family Products

Product Size CAT.# Price Quantity
BBMVEC RNA: Total RNA prepared from Bovine Brain Microvascular Endothelial Cells Size: 10 ug CAT.#: B840-R10 Price: $457.41
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BBMVEC RNA: Total RNA prepared from Bovine Brain Microvascular Endothelial Cells Size: 25 ug CAT.#: B840-R25 Price: $914.81
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Cell Freezing Medium: For general cryopreservation of most primary cells. Contains FBS & DMSO. Size: 50 ml CAT.#: 040-50 Price: $53.81
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Cyto-X Colorimetric Cell Counting Reagent: 500 tests Size: 1 Bottle CAT.#: 028-01 Price: $138.84
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Cyto-X Colorimetric Cell Counting Reagent: 100 tests Size: Sample CAT.#: 028-S Price: $35.88
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Cytofect™ Endothelial Cell Transfection Kit: 25 x 24-Well Rxns Size: 1 Sample Kit CAT.#: TF101KS Price: $53.76
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Cytofect™ Endothelial Cell Transfection Kit: 250 x 24-Well Rxns Size: 1 Kit CAT.#: TF101K Price: $430.50
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Subculture Reagent Kit: 100 ml each of HBSS, Trypsin/EDTA & Trypsin Neutralizing Solution Size: 1 Kit CAT.#: 090K Price: $54.89
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Resources/Documents

5 Important Cell Culture Rules

Format: PDF

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Cell Apps Flyer Nervous System

Format: PDF

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Cell Apps Flyer Brain Cells

Format: PDF

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Cell Apps Flyer Cardiovascular Cells

Format: PDF

Downoad Now
Cell Apps Flyer Endothelial Cells

Format: PDF

Downoad Now
Cell Apps Poster Primary Cells

Format: PDF

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Cell Applications Inc Brochure

Format: PDF

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Publications

2016
2015
Borros Gomez, S., F Rivero Monso and A. Cascante Cirera. 2016. POLYPEPTIDES FOR BLOOD BRAIN BARRIER TRANSPORT. Patent Application US 20150376237 A1
Kandimalla, K. 2015. NANOPARTICLES/THERANOSTIC VEHICLES. US Patent Application 20150078995 A1.
2014
2013
Agyare, E.K., S.R. Leonard, G.L. Curran, C.C. Yu, V.J. Lowe, A.K. Paravastu, J.F. Poduslo, and K.K. Kandimalla. 2013. Traffic jam at the blood-brain barrier promotes greater accumulation of Alzheimer's disease amyloid-+Ý proteins in the cerebral vasculature. Molecular pharmaceutics. 10:1557-1565.
Lisk, C., J. McCord, S. Bose, T. Sullivan, Z. Loomis, E. Nozik-Grayck, T. Schroeder, K. Hamilton, and D.C. Irwin. 2013. Nrf2 Activation: A potential strategy for the prevention of Acute Mountain Sickness: Therapeutic strategy for acute mountain sickness. Free Radical Biology and Medicine. 63:264-273.
McCord, S. Bose, T. Sullivan, Z. Loomis, E. Nozik-Grayck, T. Schroeder, K. Hamilton, and D.C. Irwin. 2013. Nrf2 Activation: A potential strategy for the prevention of Acute Mountain Sickness: Therapeutic strategy for acute mountain sickness. Free Radical Biology and Medicine. 63:264-273.
2012
Gil, E.S., L. Wu, L. Xu, and T.L. Lowe. 2012. β-Cyclodextrin-poly(β-Amino Ester) Nanoparticles for Sustained Drug Delivery across the Blood–Brain Barrier. Biomacromolecules. 13:3533-3541.
Niiya, Y., T. Abumiya, S. Yamagishi, J. Takino and M. Takeuchi. 2012. Advanced Glycation End Products Increase Permeability of Brain Microvascular Endothelial Cells through Reactive Oxygen Species–Induced Vascular Endothelial Growth Factor Expression. J Stroke & Cerebrovasc Diseases, 21:293-298.
Prades, R., S. Guerrero, E. Araya, C. Molina, E. Salas, E. Zurita, J. Selva, G. Egea, C. López-Iglesias, M. Teixidó, M.J. Kogan, and E. Giralt. 2012. Delivery of gold nanoparticles to the brain by conjugation with a peptide that recognizes the transferrin receptor. Biomaterials. 33:7194-7205.
Soni, V., K. Patel, D. Lakkaraju, and N. Puri. 2010. Protein-assisted drug delivery system for the targeted administration of active agents. Patent Application US 20100330158 A1.
Stie, J., and D. Fox. 2012a. Blood–brain barrier invasion by Cryptococcus neoformans is enhanced by functional interactions with plasmin. Microbiology. 158:240-258. 
2011
Esemuede, N., T. Lee, K. Maier, B. Sumpio, and V. Gahtan. 2011. Lovastatin Inhibits Thrombospondin-1-Induced Smooth Muscle Cell Chemotaxis. Journal of Surgical Research, 168:149-154.
Walsh, T.G., R.P. Murphy, P. Fitzpatrick, K.D. Rochfort, A.F. Guinan, A. Murphy, and P.M. Cummins. 2011. Stabilization of brain microvascular endothelial barrier function by shear stress involves VEcadherin signaling leading to modulation of pTyroccludin levels. Journal of cellular physiology. 226:3053-3063.
2010
Blasberg, J.D., C.M. Goparaju, H.I. Pass, and J.S. Donington. 2010. Lung cancer osteopontin isoforms exhibit angiogenic functional heterogeneity. The Journal of Thoracic and Cardiovascular Surgery. 139:1587-1593.
Closhen, D., B. Bender, H.J. Luhmann, and C.R.W. Kuhlmann. 2010. CRP-induced levels of oxidative stress are higher in brain than aortic endothelial cells. Cytokine. 50:117-120.
Haile, W.B., R. Echeverry, J. Wu, and M. Yepes. 2010. The interaction between tumor necrosis factor-like weak inducer of apoptosis and its receptor fibroblast growth factor-inducible 14 promotes the recruitment of neutrophils into the ischemic brain. Journal of cerebral blood flow and metabolism. 30:1147-1156.
Pyrgos, V., D. Mickiene, T. Sein, M. Cotton, A. Fransesconi, I. Mizrahi, M. Donoghue, N. Bundrant, S.-Y. Kim, M. Hardwick, S. Shoham, and T.J. Walsh. 2010. Effects of Immunomodulatory and Organism-Associated Molecules on the Permeability of an In Vitro Blood-Brain Barrier Model to Amphotericin B and Fluconazole. Antimicrobial agents and chemotherapy. 54:1305-1310.
2009
Gil, E.S., J. Li, H. Xiao, and T.L. Lowe. 2009. Quaternary Ammonium β-Cyclodextrin Nanoparticles for Enhancing Doxorubicin Permeability across the In Vitro Blood−Brain Barrier. Biomacromolecules. 10:505-516.
Kandimalla, K.K., O.G. Scott, S. Fulzele, M.W. Davidson, and J.F. Poduslo. 2009. Mechanism of neuronal versus endothelial cell uptake of Alzheimer's disease amyloid β protein. PloS one. 4:e4627.
Kuhlmann, C.R.W., L. Librizzi, D. Closhen, T. Pflanzner, V. Lessmann, C.U. Pietrzik, M. de Curtis, and H.J. Luhmann. 2009. Mechanisms of C-Reactive Protein-Induced Blood–Brain Barrier Disruption. Stroke; a journal of cerebral circulation. 40:1458-1466.
2008
Agyare, E.K., G.L. Curran, M. Ramakrishnan, C.Y. Caroline, J.F. Poduslo, and K.K. Kandimalla. 2008. Development of a smart nano-vehicle to target cerebrovascular amyloid deposits and brain parenchymal plaques observed in Alzheimer’s disease and cerebral amyloid angiopathy. Pharm Res. 25:2674-2684.
Colgan, O.C., N.T. Collins, G. Ferguson, R.P. Murphy, Y.A. Birney, P.A. Cahill, and P.M. Cummins. 2008. Influence of basolateral condition on the regulation of brain microvascular endothelial tight junction properties and barrier function. Brain research. 1193:84-92.
Gil, E., and T. Lowe. 2008. Invention of Polysaccharide-based Nanopa rticles for Enhancing Drug Permeability across the Blood Brain Barrier. NSTI-Nanotech, 2:379-381.
Kuhlmann, C.R.W., M. Gerigk, B. Bender, D. Closhen, V. Lessmann, and H.J. Luhmann. 2008. Fluvastatin prevents glutamate-induced blood-brain-barrier disruption in vitro. Life sciences. 82:1281-1287.
Yang, H., S. Lopina, L. DiPersio, and S. Schmidt. 2008. Stealth dendrimers for drug delivery: correlation between PEGylation, cytocompatibility, and drug payload. J Mater Sci: Mater Med. 19:1991-1997.
2007
Colgan, O.C., G. Ferguson, N.T. Collins, R.P. Murphy, G. Meade, P.A. Cahill, and P.M. Cummins. 2007. Regulation of bovine brain microvascular endothelial tight junction assembly and barrier function by laminar shear stress. American Journal of Physiology-Heart and Circulatory Physiology. 292:H3190-H3197.
Erdogan, A., A.K. Most, B. Wienecke, A. Fehsecke, C. Leckband, R. Voss, M.T. Grebe, H. Tillmanns, C.A. Schaefer, and C.R.W. Kuhlmann. 2007. Apigenin-induced nitric oxide production involves calcium-activated potassium channels and is responsible for antiangiogenic effects. Journal of Thrombosis and Haemostasis. 5:1774-1781.
Kuhlmann, C.R.W., R. Tamaki, M. Gamerdinger, V. Lessmann, C. Behl, O.S. Kempski, and H.J. Luhmann. 2007. Inhibition of the myosin light chain kinase prevents hypoxia-induced blood–brain barrier disruption. Journal of Neurochemistry. 102:501-507.
Tang, Y., T. Han, M. Everts, Z. Zhu, G. Gillespie, D. Curiel, and H. Wu. 2007. Directing adenovirus across the blood–brain barrier via melanotransferrin (P97) transcytosis pathway in an in vitro model. Gene Therapy, 14:523-532.
2006
Colgan, O. 2006. Factors affecting microvascular endothelial tight junction assembly and barrier function in the blood-brain barrier. Dublin City University, PhD dissertation.
Motz, G.T., M. Zuccarello, and R.M. Rapoport. 2006. Alkaline pH-Induced Extracellular Regulated Protein Kinase Activation in Brain Microvascular Endothelial Cells: Differential Effects of Tris and Lowered CO2. Endothelium. 13:313-316.
Niiya, Y., T. Abumiya, H. Shichinohe, S. Kuroda, S. Kikuchi, M. Ieko, S.-i. Yamagishi, M. Takeuchi, T. Sato, and Y. Iwasaki. 2006. Susceptibility of brain microvascular endothelial cells to advanced glycation end products-induced tissue factor upregulation is associated with intracellular reactive oxygen species. Brain research. 1108:179-187.
2003
Kitamuro, T., K. Takahashi, K. Ogawa, R. Udono-Fujimori, K. Takeda, K. Furuyama, M. Nakayama, J. Sun, H. Fujita, W. Hida, T. Hattori, K. Shirato, K. Igarashi, and S. Shibahara. 2003. Bach1 Functions as a Hypoxia-inducible Repressor for the Heme Oxygenase-1 Gene in Human Cells. Journal of Biological Chemistry. 278:9125-9133.