ArticleBlood advances2017
ICAM-1-targeted thrombomodulin mitigates tissue factor-driven inflammatory thrombosis in a human endothelialized microfluidic model.
Article in Blood advances, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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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.
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Who cites it
25 citing papers in PubMed, 38 citations in OpenAlex.
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- High glucose enhances inflammation-driven platelet adhesion to endothelial cells in vitro.Scientific reports · 2025Article
- New Cellular Models to Support Preclinical Studies on ICAM-1-Targeted Drug Delivery.Journal of drug delivery science and technology · 2024Article
- Vascular dysfunction in hemorrhagic viral fevers: opportunities for organotypic modeling.Biofabrication · 2024Review
- Proteomic profiling identifies novel proteins for genetic risk of severe COVID-19: the Atherosclerosis Risk in Communities Study.Human molecular genetics · 2022Article
- Targeting vascular inflammation through emerging methods and drug carriers.Advanced drug delivery reviews · 2022Review
- Red blood cells: The metamorphosis of a neglected carrier into the natural mothership for artificial nanocarriers.Advanced drug delivery reviews · 2021Review
- Red Blood Cell Hitchhiking: A Novel Approach for Vascular Delivery of Nanocarriers.Annual review of biomedical engineering · 2021Article
- Optimisation and validation of immunohistochemistry protocols for cancer research.Histology and histopathology · 2021Article
- ICAM-1 Activates Platelets and Promotes Endothelial Permeability through VE-Cadherin after Insufficient Radiofrequency Ablation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Thromboinflammation Model-on-A-Chip by Whole Blood Microfluidics on Fixed Human Endothelium.Diagnostics (Basel, Switzerland) · 2021Article
- A hybridoma-derived monoclonal antibody with high homology to the aberrant myeloma light chain.PloS one · 2021Article
- The role of antibody expression and their association with bladder cancer recurrence: a single-centre prospective clinical-pilot study in 35 patients.BMC urology · 2020Article
- Endothelial cells, neutrophils and platelets: getting to the bottom of an inflammatory triangle.Open biology · 2020Review
- Bivalent engagement of endothelial surface antigens is critical to prolonged surface targeting and protein delivery in vivo.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Localized endothelial-based control of platelet aggregation and coagulation under flow: A proof-of-principle vessel-on-a-chip study.Journal of thrombosis and haemostasis : JTH · 2020Article
- Selective targeting of nanomedicine to inflamed cerebral vasculature to enhance the blood-brain barrier.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Vascular Targeting of Radiolabeled Liposomes with Bio-Orthogonally Conjugated Ligands: Single Chain Fragments Provide Higher Specificity than Antibodies.Bioconjugate chemistry · 2018Article
- Sepsis-induced thrombus formation and cell-specific HIFs.Thrombosis research · 2018Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Diverse human illnesses are characterized by loss or inactivation of endothelial thrombomodulin (TM), predisposing to microvascular inflammation, activation of coagulation, and tissue ischemia. Single-chain antibody fragment (scFv)/TM) fusion proteins, previously protective against end-organ injury in murine models of inflammation, are attractive candidates to treat inflammatory thrombosis. However, animal models have inherent differences in TM and coagulation biology, are limited in their ability to resolve and control endothelial biology, and do not allow in-depth testing of "humanized" scFv/TM fusion proteins, which are necessary for translation to the clinical domain. To address these challenges, we developed a human whole-blood, microfluidic model of inflammatory, tissue factor (TF)-driven coagulation that features a multichannel format for head-to-head comparison of therapeutic approaches. In this model, fibrin deposition, leukocyte adhesion, and platelet adhesion and aggregation showed a dose-dependent response to tumor necrosis factor-α activation and could be quantified via real-time microscopy. We used this model to compare hTM/R6.5, a humanized, intracellular adhesion molecule 1 (ICAM-1)-targeted scFv/TM biotherapeutic, to untargeted antithrombotic agents, including soluble human TM (shTM), anti-TF antibodies, and hirudin. The targeted hTM/R6.5 more effectively inhibited TF-driven coagulation in a protein C (PC)-dependent manner and demonstrated synergy with supplemental PC. These results support the translational prospects of ICAM-targeted scFv/TM and illustrate the utility of the microfluidic system as a platform to study humanized therapeutics at the interface of endothelium and whole blood under flow.
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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.