Evidence map›Paper›PMID 23068604›Full record

ArticleJournal of neuroscience methods2013

Immortalized human cerebral microvascular endothelial cells maintain the properties of primary cells in an in vitro model of immune migration across the blood brain barrier.

Brian P Daniels, Lillian Cruz-Orengo, Tracy Jo Pasieka, Pierre-Olivier Couraud, Ignacio A Romero, Babette Weksler, John A Cooper, Tamara L Doering, Robyn S Klein

Registry-linked trialAbstract read
In one paragraph

Article in Journal of neuroscience methods, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02653196 (A Multi-Institutional Pilot Study of Allogeneic Hematopoietic Stem Cell Transplantation for Patients With Malignant Neuro-Epithelial and Other Solid Tumors), which is not on this map. Cited by 72 papers.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed
3.8field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02653196 early_phase1terminatednot on this mapstarted 2015, after this paper: background citation

A Multi-Institutional Pilot Study of Allogeneic Hematopoietic Stem Cell Transplantation for Patients With Malignant Neuro-Epithelial and Other Solid Tumors

TypeinterventionalSponsorMontefiore Medical CenterRan2015 to 2017Enrolled1ConditionsNeuroepithelial Tumor, Solid Tumor, Allogeneic Hematopoietic Stem Cell TransplantationArmsAllogeneic hematopoietic stem cell transplant following thiotepa-based marrow ablative chemotherapy, Keratinocyte Growth Factor, Alemtuzumab, Thiotepa, Etoposide
3 · Its place in the literature

Who cites it

72 citing papers in PubMed, 124 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026
    Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Engineering in vitro vascular microsystems.Microsystems & nanoengineering · 2025
    Review
  12. Article
  13. 3DFrontiers in pharmacology · 2025
    Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article

12 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 3 countries.

Brian P DanielsDepartment of Anatomy and Neurobiology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
Lillian Cruz-Orengo
Tracy Jo Pasieka
Pierre-Olivier Couraud
Ignacio A Romero
Babette Weksler
John A Cooper
Tamara L Doering
Robyn S Klein
Washington University in St. Louis · USCornell University · USThe Open University · GBUniversité Paris Cité · FR

Funding

Virology and Smallpox VaccinationsU54AI057160 · NIAID · WASHINGTON UNIVERSITY · PI RAY, RANJIT · 2003 to 2013
$80.9M
Validating diffusion MRI biomarkers of inflammation and axon pathologies in EAEP01NS059560 · NINDS · WASHINGTON UNIVERSITY · PI SONG, SHENG-KWEI · 2008 to 2018
$11.3M
Molecular Mechanisms in Actin Assembly &Cell MotilityR01GM038542 · NIGMS · WASHINGTON UNIVERSITY · PI COOPER, JOHN A · 1989 to 2013
$7.4M
Neuroprotection and repair during West Nile Virus EncephalitisR01NS052632 · NINDS · WASHINGTON UNIVERSITY · PI KLEIN, ROBYN S. · 2005 to 2020
$5.0M
CRYPTOCOCCAL INTERACTIONS WITH HOST CELLSR01AI078795 · NIAID · WASHINGTON UNIVERSITY · PI DOERING, TAMARA L · 2009 to 2013
$2.0M
NIAID NIH HHS R01 AI078795NIAID NIH HHS U54 AI057160NIGMS NIH HHS R01 GM038542NINDS NIH HHS 1F32NS0748424-01NINDS NIH HHS P01 NS059560NINDS NIH HHS R01 NS052632
6 · The paper itself

Abstract

The immortalized human cerebral microvascular endothelial cell line HCMEC/D3 presents a less expensive and more logistically feasible alternative to primary human brain microvascular endothelial cells (HBMEC's) for use in constructing in vitro models of the blood brain barrier (BBB). However, the fidelity of the HCMEC/D3 cell line to primary HBMEC's in studies of immune transmigration has yet to be established. Flow cytometric analysis of primary human leukocyte migration across in vitro BBB's generated with either HCMEC/D3 or primary HBMEC's revealed that HCMEC/D3 maintains the immune barrier properties of primary HBMEC's. Leukocyte migration responses and inflammatory cytokine production were statistically indistinguishable between both endothelial cell types, and both cell types responded similarly to astrocyte coculture, stimulation of leukocytes with phorbol myristate acetate (PMA) and ionomycin, and inflammatory cytokine treatment. This report is the first to validate the HCMEC/D3 cell line in a neuroimmunological experimental system via direct comparison to primary HBMEC's, demonstrating remarkable fidelity in terms of barrier resistance, immune migration profiles, and responsiveness to inflammatory cytokines. Moreover, we report novel findings demonstrating that interaction effects between immune cells and resident CNS cells are preserved in HCMEC/D3, suggesting that important characteristics of neuroimmune interactions during CNS inflammation are preserved in systems utilizing this cell line. Together, these findings demonstrate that HCMEC/D3 is a valid and powerful tool for less expensive and higher throughput in vitro investigations of immune migration at the BBB.

Indexed as

Models, BiologicalAnalysis of VarianceArea Under CurveAstrocytesBlood-Brain BarrierCalcium IonophoresCell MovementCells, CulturedCerebral CortexCoculture TechniquesCytokinesDiffusion Chambers, CultureEndothelial CellsFlow CytometryHumansIonomycinCalcium IonophoresCytokinesIonomycinPhenobarbitalTetradecanoylphorbol Acetate

Identifiers

PMID23068604
PMCPMC3641664
OpenAlexW2042938829

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.