Endothelial inflammation and neutrophil transmigration are modulated by extracellular matrix composition in an inflammation-on-a-chip model

Riddle, Rebecca; Jennbacken, Karin; Hansson, Kenny M.; Harper, Matthew T.

doi:10.1038/s41598-022-10849-x

Cited by 25 publications

(22 citation statements)

References 110 publications

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“…1a,bi,ci). The liquidgel interface between the two channels acted as a physical barrier that prevented neutrophils from migrating into the gel channel and thus helped maintain the "separated" nature of the scenario 42,43 . We demonstrated that 10kDa uorescein-dextran can diffuse from the central channel into the tumor gel channel within 1 h and from the tumor gel channel into the central channel within 1 h (Supplementary Fig.…”

Section: Design Characterization and Validation Of The Nti-chipmentioning

confidence: 99%

A microphysiological system reveals neutrophil contact-dependent attenuation of pancreatic tumor progression by CXCR2 inhibition-based immunotherapy

Shao,

Delk,

Jones

2023

Preprint

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Cancer cells recruit neutrophils from the bloodstream into the tumor tissue, where these immune cells promote the progression of numerous solid tumors. Studies in mice suggest that blocking neutrophil recruitment to tumors by inhibition of neutrophil chemokine receptor CXCR2 could be a potential immunotherapy for pancreatic cancer. Yet, the mechanisms by which neutrophils promote tumor progression in humans, as well as how CXCR2 inhibition could potentially serve as a cancer therapy, remain elusive. In this study, we developed a human cell-based microphysiological system to quantify neutrophil-tumor spheroid interactions in both “separated” and “contact” scenarios. We found that neutrophils promote the invasion of tumor spheroids through the secretion of soluble factors and direct contact with cancer cells. However, they promote the proliferation of tumor spheroids solely through direct contact. Interestingly, treatment with AZD-5069, a CXCR2 inhibitor, attenuates invasion and proliferation of tumor spheroids by blocking direct contact with neutrophils. Our findings show that CXCR2 inhibition reduces neutrophil migration toward tumor spheroids. These results shed new light on the tumor-promoting mechanisms of human neutrophils and the tumor-suppressive mechanisms of CXCR2 inhibition in pancreatic cancer and may aid in the design and optimization of novel immunotherapeutic strategies based on neutrophils.

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Section: Design Characterization and Validation Of The Nti-chipmentioning

confidence: 99%

A microphysiological system reveals neutrophil contact-dependent attenuation of pancreatic tumor progression by CXCR2 inhibition-based immunotherapy

Shao,

Delk,

Jones

2023

Preprint

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“…In addition, thanks to a microfluidic system under flow, Arts et al shed light on the existence of “hotspots” with enrichment in PECAM-1 and ICAM-1 adhesive molecules at junctional membrane protrusions between endothelial cells, where neutrophils preferentially undergo diapedesis after crawling along the junction up to these specific sites [ 72 ]. Moreover, a study based on an inflammation-on-a-chip model revealed that the ECM composition modulated the capacity of neutrophils to undergo diapedesis in response to TNFα, with an exacerbated transmigration occurring in vessels grown in basement membrane extract gels [ 73 ].…”

Section: Chips Patrolling To Catch Specific Scenes Of the Bloody Cons...mentioning

confidence: 99%

A Bloody Conspiracy— Blood Vessels and Immune Cells in the Tumor Microenvironment

Terrassoux

Claux

Bacari

et al. 2022

Cancers

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Cancer progression occurs in concomitance with a profound remodeling of the cellular microenvironment. Far from being a mere passive event, the re-orchestration of interactions between the various cell types surrounding tumors highly contributes to the progression of the latter. Tumors notably recruit and stimulate the sprouting of new blood vessels through a process called neo-angiogenesis. Beyond helping the tumor cope with an increased metabolic demand associated with rapid growth, this also controls the metastatic dissemination of cancer cells and the infiltration of immune cells in the tumor microenvironment. To decipher this critical interplay for the clinical progression of tumors, the research community has developed several valuable models in the last decades. This review offers an overview of the various instrumental solutions currently available, including microfluidic chips, co-culture models, and the recent rise of organoids. We highlight the advantages of each technique and the specific questions they can address to better understand the tumor immuno-angiogenic ecosystem. Finally, we discuss this development field’s fundamental and applied perspectives.

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“…PMN migratory function in response to inflammatory stimuli or environmental conditions is frequently modeled on tissue chip platforms ( 61 , 225 – 227 ). Because of their short lifespan, PMNs are most commonly isolated from whole blood via density gradient separation and used immediately ( Table 4 ).…”

Section: Immune Cellsmentioning

confidence: 99%

Sourcing cells for in vitro models of human vascular barriers of inflammation

McCloskey

Zhang²,

Ahmad³

et al. 2022

Front. Med. Technol.

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The vascular system plays a critical role in the progression and resolution of inflammation. The contributions of the vascular endothelium to these processes, however, vary with tissue and disease state. Recently, tissue chip models have emerged as promising tools to understand human disease and for the development of personalized medicine approaches. Inclusion of a vascular component within these platforms is critical for properly evaluating most diseases, but many models to date use “generic” endothelial cells, which can preclude the identification of biomedically meaningful pathways and mechanisms. As the knowledge of vascular heterogeneity and immune cell trafficking throughout the body advances, tissue chip models should also advance to incorporate tissue-specific cells where possible. Here, we discuss the known heterogeneity of leukocyte trafficking in vascular beds of some commonly modeled tissues. We comment on the availability of different tissue-specific cell sources for endothelial cells and pericytes, with a focus on stem cell sources for the full realization of personalized medicine. We discuss sources available for the immune cells needed to model inflammatory processes and the findings of tissue chip models that have used the cells to studying transmigration.

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Endothelial inflammation and neutrophil transmigration are modulated by extracellular matrix composition in an inflammation-on-a-chip model

Cited by 25 publications

References 110 publications

A microphysiological system reveals neutrophil contact-dependent attenuation of pancreatic tumor progression by CXCR2 inhibition-based immunotherapy

A microphysiological system reveals neutrophil contact-dependent attenuation of pancreatic tumor progression by CXCR2 inhibition-based immunotherapy

A Bloody Conspiracy— Blood Vessels and Immune Cells in the Tumor Microenvironment

Sourcing cells for in vitro models of human vascular barriers of inflammation

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