ArticleProceedings of the National Academy of Sciences of the United States of America2023
A 3D biomimetic model of lymphatics reveals cell-cell junction tightening and lymphedema via a cytokine-induced ROCK2/JAM-A complex.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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Who cites it
16 citing papers in PubMed, 17 citations in OpenAlex.
- A 3D microfluidic model of exchange between perfused blood and lymphatic microvascular networks.Lab on a chip · 2026Article
- A Versatile Microfluidic Extrusion-Based Hydrogel Platform for Self-Organization and Long-Term Maintenance of Engineered 3D Lymphatic Endothelium.Advanced healthcare materials · 2026Article
- Fluid Forces Control Structural Remodeling of Blind-Ended Lymphatic Microvessels.Advanced healthcare materials · 2026Article
- SIRT5 acts in the tumor microenvironment via endothelial cell metabolism to support breast cancer growth.bioRxiv : the preprint server for biology · 2026Article
- Lymphatics-on-a-chip microphysiological system: engineering lymphatic structure and functionLab on a chip · 2026Review
- Blocking glutamine transport normalizes lymphatic vessels in hypoxic environments by attenuating glycolysis.bioRxiv : the preprint server for biology · 2026Article
- Microphysiological Systems of Lymphatics and Immune Organs.Advanced healthcare materials · 2026Review
- AI-Empowered Mechanomedicine for Cancer-Related Lymphedema.Research (Washington, D.C.) · 2026Review
- Organ-on-chip platforms for nanoparticle toxicity and efficacy assessment: Advancing beyond traditional in vitro and in vivo models.Materials today. Bio · 2025Review
- Understanding the Lymphatic System: Tissue-on-Chip Modeling.Annual review of biomedical engineering · 2025Review
- Characteristics and advances in signaling pathways, cellular communication, cell junctions, and oxidative stress in lymphedema.Frontiers in cell and developmental biology · 2025Review
- Three-Dimensional Lymphatics-on-a-Chip Reveals Distinct, Size-Dependent Nanoparticle Transport Mechanisms in Lymphatic Drug Delivery.ACS biomaterials science & engineering · 2024Article
- The Edifice of Vasculature-On-Chips: A Focused Review on the Key Elements and Assembly of Angiogenesis Models.ACS biomaterials science & engineering · 2024Review
- Mimicking blood and lymphatic vasculatures using microfluidic systems.Biomicrofluidics · 2024Review
- TRPML1 acts as a predisposing factor in lymphedema development by regulating the subcellular localization of aquaporin-3, -5.PloS one · 2024Article
- Robust Differentiation of Human Pluripotent Stem Cells into Lymphatic Endothelial Cells Using Transcription Factors.Cells, tissues, organs · 2024Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
Impaired lymphatic drainage and lymphedema are major morbidities whose mechanisms have remained obscure. To study lymphatic drainage and its impairment, we engineered a microfluidic culture model of lymphatic vessels draining interstitial fluid. This lymphatic drainage-on-chip revealed that inflammatory cytokines that are known to disrupt blood vessel junctions instead tightened lymphatic cell-cell junctions and impeded lymphatic drainage. This opposing response was further demonstrated when inhibition of rho-associated protein kinase (ROCK) was found to normalize fluid drainage under cytokine challenge by simultaneously loosening lymphatic junctions and tightening blood vessel junctions. Studies also revealed a previously undescribed shift in ROCK isoforms in lymphatic endothelial cells, wherein a ROCK2/junctional adhesion molecule-A (JAM-A) complex emerges that is responsible for the cytokine-induced lymphatic junction zippering. To validate these in vitro findings, we further demonstrated in a genetic mouse model that lymphatic-specific knockout of ROCK2 reversed lymphedema in vivo. These studies provide a unique platform to generate interstitial fluid pressure and measure the drainage of interstitial fluid into lymphatics and reveal a previously unappreciated ROCK2-mediated mechanism in regulating lymphatic drainage.
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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.