Linking lymphatic function to disease

Murfee, Walter L.; Breslin, Jerome W.

doi:10.1113/jp280096

Cited by 3 publications

(3 citation statements)

References 2 publications

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“…As mentioned above, lymphatic barrier function or permeability plays a key role in lymphatic drainage processes. Thus, deciphering lymphatic barrier function and its regulation is crucial for understanding physiological lymphatic functions, such as lipid transport, metabolism, and immune regulation, 35–39 and the pathology of lymphatic diseases 4,27,31,40,41 . LV barrier function can be influenced by numerous factors, including extracellular matrices (ECM), 42 endothelial cell‐cell junctions, 43 endocytosis, 44 lymph flow, 45,46 lymphatic smooth muscle cell engagement, 28 and interaction with other conditions, such as inflammation 47–49 .…”

Section: Introductionmentioning

confidence: 99%

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

2021

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Objective 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. Methods 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. Results 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. Conclusions 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.

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Section: Introductionmentioning

confidence: 99%

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

2021

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“…Lymphatic research has rapidly accelerated and evolved over the last few decades with more clinicians and basic scientists appreciating the huge impact of this vasculature. 1 The lymphatic system, with its network of vessels and interconnected nodes, returns interstitial fluid to the blood circulation and is central in the maintenance of fluid homeostasis, immune surveillance, and uptake of dietary lipids. 2,3 The development of cutting-edge genetic models and imaging tools to manipulate and visualize lymphatic vessels, coupled with bioengineering approaches applied to the fundamental physiology of lymphatic vessel function, has significantly impacted our current understanding of the critical roles played by lymphatics both during development and in pathophysiological conditions across a plethora of disease states.…”

Section: E D I T O R I a L Lymphatic Pathophysiologymentioning

confidence: 99%

“…Lymphatic research has rapidly accelerated and evolved over the last few decades with more clinicians and basic scientists appreciating the huge impact of this vasculature 1 . The lymphatic system, with its network of vessels and interconnected nodes, returns interstitial fluid to the blood circulation and is central in the maintenance of fluid homeostasis, immune surveillance, and uptake of dietary lipids 2,3 .…”

mentioning

confidence: 99%