A microfluidic device for assessment of E-selectin-mediated neutrophil recruitment to inflamed endothelium and prediction of therapeutic response in sickle cell disease

Man, Yuncheng; Kucukal, Erdem; Liu, Shichen; An, Ran; Goreke, Utku; Wulftange, William J.; Sekyonda, Zoe; Bode, Allison; Little, Jane A.; Manwani, Deepa; Stavrou, Evi X.; Gürkan, Umut A.

doi:10.1016/j.bios.2022.114921

Cited by 4 publications

(4 citation statements)

References 53 publications

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“…Development of “organ-on-chip” assays, also known as microphysiological systems or 3-D biomimetic microfluidic assays, offer a number of advantages including the ability to observe and measure in real time neutrophil-endothelial cell interactions such as chemotaxis, upregulation of adhesion molecules and changes in response to various therapeutic agents ( Ren et al., 2022 ; Man et al., 2023 ). The ability to use primary human cells in microphysiological systems increases their clinical relevance.…”

Section: Emerging In Vitro Models – the Promise Of...mentioning

confidence: 99%

The critical role of neutrophil-endothelial cell interactions in sepsis: new synergistic approaches employing organ-on-chip, omics, immune cell phenotyping and in silico modeling to identify new therapeutics

Liu,

Langston,

Prabhakarpandian

et al. 2024

Front. Cell. Infect. Microbiol.

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Sepsis is a global health concern accounting for more than 1 in 5 deaths worldwide. Sepsis is now defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis can develop from bacterial (gram negative or gram positive), fungal or viral (such as COVID) infections. However, therapeutics developed in animal models and traditional in vitro sepsis models have had little success in clinical trials, as these models have failed to fully replicate the underlying pathophysiology and heterogeneity of the disease. The current understanding is that the host response to sepsis is highly diverse among patients, and this heterogeneity impacts immune function and response to infection. Phenotyping immune function and classifying sepsis patients into specific endotypes is needed to develop a personalized treatment approach. Neutrophil-endothelium interactions play a critical role in sepsis progression, and increased neutrophil influx and endothelial barrier disruption have important roles in the early course of organ damage. Understanding the mechanism of neutrophil-endothelium interactions and how immune function impacts this interaction can help us better manage the disease and lead to the discovery of new diagnostic and prognosis tools for effective treatments. In this review, we will discuss the latest research exploring how in silico modeling of a synergistic combination of new organ-on-chip models incorporating human cells/tissue, omics analysis and clinical data from sepsis patients will allow us to identify relevant signaling pathways and characterize specific immune phenotypes in patients. Emerging technologies such as machine learning can then be leveraged to identify druggable therapeutic targets and relate them to immune phenotypes and underlying infectious agents. This synergistic approach can lead to the development of new therapeutics and the identification of FDA approved drugs that can be repurposed for the treatment of sepsis.

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Section: Emerging In Vitro Models – the Promise Of...mentioning

confidence: 99%

The critical role of neutrophil-endothelial cell interactions in sepsis: new synergistic approaches employing organ-on-chip, omics, immune cell phenotyping and in silico modeling to identify new therapeutics

Liu,

Langston,

Prabhakarpandian

et al. 2024

Front. Cell. Infect. Microbiol.

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“…E-selectin plays a critical role in the adhesion of leukocytes to the endothelium during inflammation, a process facilitated by its interaction with specific carbohydrate ligands on the surface of these cells. This E-selectin/E-selectin ligand axis is a prime target for therapeutic intervention, aiming to disrupt the inflammatory cascade at its inception ( 10 ). The interaction mediated by E-selectin offers potential therapeutic avenues for addressing various diseases.…”

Section: Therapeutic Approaches Targeting E-selectinmentioning

confidence: 99%

“…E-selectin belongs to the selectin family which is featured by homologous derived N-terminal determinants and all bind to similar fucosylated or sialylated glycan ligands ( 9 ). E-selectin interaction with its ligands contributes to acute and chronic inflammation, offering potential therapeutic avenues for addressing various diseases ( 10 ). The selectins, including P-selectin and L-selectin, share similar residues in spatial distributions with different performance in physiological activities.…”

Section: Introductionmentioning

confidence: 99%

E-selectin in vascular pathophysiology

Zhang,

Huang,

Zhu

et al. 2024

Front. Immunol.

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Selectins are a group of Ca2+-dependent, transmembrane type I glycoproteins which attract cell adhesion and migration. E-selectin is exclusively expressed in endothelial cells, and its expression is strongly enhanced upon activation by pro-inflammatory cytokines. The interaction of E-selectin with its ligands on circulating leukocytes captures and slows them down, further facilitating integrin activation, firm adhesion to endothelial cells and transmigration to tissues. Oxidative stress induces endothelial cell injury, leading to aberrant expression of E-selectin. In addition, the elevated level of E-selectin is positively related to high risk of inflammation. Dysregulation of E-selectin has been found in several pathological conditions including acute kidney injury (AKI), pulmonary diseases, hepatic pathology, Venous thromboembolism (VTE). Deletion of the E-selectin gene in mice somewhat ameliorates these complications. In this review, we describe the mechanisms regulating E-selectin expression, the interaction of E-selectin with its ligands, the E-selectin physiological and pathophysiological roles, and the therapeutical potential of targeting E-selectin.

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“…In current clinical laboratory settings, RBCs are typically analyzed by ektacytometry, [26][27][28][29] or in microfluidic channels lined with endothelial cells or functionalized with endothelialassociated proteins. [30][31][32][33][34][35][36] Ektacytometry provides a bulk average, and therefore it is limited by its ability to measure deformability of individual cells. 28 Microchannels designed for adhesion measurement are typically at least one order of magnitude larger than the red cell dimension (>50 μm) and therefore present limitations in providing measurement of RBCs perfusing through microcapillaries.…”

Section: Introductionmentioning

confidence: 99%

Microfluidic concurrent assessment of red blood cell adhesion and microcapillary occlusion: potential hemorheological biomarkers in sickle cell disease

Man

et al. 2023

Sens. Diagn.

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A microfluidic device for assessment of E-selectin-mediated neutrophil recruitment to inflamed endothelium and prediction of therapeutic response in sickle cell disease

Cited by 4 publications

References 53 publications

The critical role of neutrophil-endothelial cell interactions in sepsis: new synergistic approaches employing organ-on-chip, omics, immune cell phenotyping and in silico modeling to identify new therapeutics

The critical role of neutrophil-endothelial cell interactions in sepsis: new synergistic approaches employing organ-on-chip, omics, immune cell phenotyping and in silico modeling to identify new therapeutics

E-selectin in vascular pathophysiology

Microfluidic concurrent assessment of red blood cell adhesion and microcapillary occlusion: potential hemorheological biomarkers in sickle cell disease

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