Evidence map›Paper›PMID 34569678›Full record

ArticleMicrocirculation (New York, N.Y. : 1994)2021

A bioengineered lymphatic vessel model for studying lymphatic endothelial cell-cell junction and barrier function.

Aria R Henderson, Isabelle S Ilan, Esak Lee

Open access · greenAbstract read
In one paragraph

Article in Microcirculation (New York, N.Y. : 1994), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
3.5field-weighted citation impact, top 5% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

40 citing papers in PubMed, 51 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Review
  9. Review
  10. Endothelial glycocalyx glycan expression in lymphatic vasculature in mice.Frontiers in cell and developmental biology · 2026
    Article
  11. Review
  12. Microphysiological systems for metastasis research: a stepwise approach.Cellular oncology (Dordrecht, Netherlands) · 2025
    Review
  13. Review
  14. Understanding the Lymphatic System: Tissue-on-Chip Modeling.Annual review of biomedical engineering · 2025
    Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Review
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

3 authors at 2 institutions in 1 country.

Aria R HendersonNancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York, USA.
Isabelle S IlanCollege of Human Ecology, Cornell University, Ithaca, New York, USA.
Esak LeeNancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York, USA.
Cornell University · USNew York State University College of Human Ecology · US

Funding

Tissue-Engineered Models of Lymphatic Drainage in Breast CancerR01CA279560 · NCI · CORNELL UNIVERSITY · PI Esak Lee · 2023 to 2026
$1.6M
A Bioengineered Model of Tumor Vessel Interactions in Pancreatic CancerR21CA252162 · NCI · CORNELL UNIVERSITY · PI LEE, ESAK · 2022 to 2023
$401k
A Bioengineered Model for Deciphering Lymphatic Dysfunction in InflammationR21AI166772 · NIAID · CORNELL UNIVERSITY · PI LEE, ESAK · 2021 to 2022
$400k
NCI NIH HHS R01 CA279560NCI NIH HHS R21 CA252162NIAID NIH HHS R21 AI166772
6 · The paper itself

Abstract

objectiveLymphatic vessels (LVs) maintain fluid homeostasis by draining interstitial fluid. A failure in lymphatic drainage triggers lymphatic diseases such as lymphedema. Since lymphatic drainage is regulated by lymphatic barrier function, developing experimental models that assess lymphatic barrier function is critical for better understanding of lymphatic physiology and disease.

methodsWe built a lymphatic vessel-on-chip (LV-on-chip) by fabricating a microfluidic device that includes a hollow microchannel embedded in three-dimensional (3D) hydrogel. Employing luminal flow in the microchannel, human lymphatic endothelial cells (LECs) seeded in the microchannel formed an engineered LV exhibiting 3D conduit structure.

resultsLymphatic endothelial cells formed relatively permeable junctions in 3D collagen 1. However, adding fibronectin to the collagen 1 apparently tightened LEC junctions. We tested lymphatic barrier function by introducing dextran into LV lumens. While LECs in collagen 1 showed permeable barriers, LECs in fibronectin/collagen 1 showed reduced permeability, which was reversed by integrin α5 inhibition. Mechanistically, LECs expressed inactivated integrin α5 in collagen 1. However, integrin α5 is activated in fibronectin and enhances barrier function. Integrin α5 activation itself also tightened LEC junctions in the absence of fibronectin.

conclusionsLymphatic vessel-on-chip reveals integrin α5 as a regulator of lymphatic barrier function and provides a platform for studying lymphatic barrier function in various conditions.

Indexed as

Lymphatic VesselsLymphedemaEndothelial CellsEndothelium, LymphaticHumansIntercellular Junctions3D bioengineered modelsintegrin α5junctionsLV-on-chiplymphatic barrier functionlymphatic endothelial cells

Identifiers

PMID34569678
PMCPMC9274261
OpenAlexW3202958382

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.