A bioengineered lymphatic vessel model for studying lymphatic endothelial cell-cell junction and barrier function.
3D bioengineered models
LV-on-chip
integrin α5
junctions
lymphatic barrier function
lymphatic endothelial cells
Journal
Microcirculation (New York, N.Y. : 1994)
ISSN: 1549-8719
Titre abrégé: Microcirculation
Pays: United States
ID NLM: 9434935
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
revised:
09
09
2021
received:
04
05
2021
accepted:
20
09
2021
pubmed:
28
9
2021
medline:
25
3
2022
entrez:
27
9
2021
Statut:
ppublish
Résumé
Lymphatic 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. We 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. Lymphatic 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. Lymphatic 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.
Identifiants
pubmed: 34569678
doi: 10.1111/micc.12730
pmc: PMC9274261
mid: NIHMS1820297
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e12730Subventions
Organisme : NIAID NIH HHS
ID : R21 AI166772
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA252162
Pays : United States
Informations de copyright
© 2021 John Wiley & Sons Ltd.
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