Two-way communication between<i>ex vivo</i>tissues on a microfluidic chip: application to tumor–lymph node interaction

Shim, Sangjo; Belanger, Maura C.; Harris, Audray K.; Munson, Jennifer M.; Pompano, Rebecca R.

doi:10.1039/c8lc00957k

Cited by 79 publications

(95 citation statements)

References 66 publications

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“…This LNoC model thus allowed for the investigation of pMHC–T-cell receptor bonding mechanisms under controlled microenvironmental conditions. More studies have been performed to evaluate DC–T-cell interactions using LNoC models that were introduced in Table 1 [ 49 , 50 ].…”

Section: State-of-the-art Immune-system-on-a-chip Modelsmentioning

confidence: 99%

“…However, in some cases, there is no need to overcomplicate the device design. In those cases, simplifying the (patho)physiology is equally important as answering the relevant biologic questions, as shown by several studies [ 25 , 50 , 106 , 112 ]. Thus, researchers should be careful to avoid both oversimplifying the in vivo (patho)physiology, as well as overcomplicating the device design.…”

Section: Limitations and Future Perspectivesmentioning

confidence: 99%

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Immune Organs and Immune Cells on a Chip: An Overview of Biomedical Applications

et al. 2020

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Understanding the immune system is of great importance for the development of drugs and the design of medical implants. Traditionally, two-dimensional static cultures have been used to investigate the immune system in vitro, while animal models have been used to study the immune system’s function and behavior in vivo. However, these conventional models do not fully emulate the complexity of the human immune system or the human in vivo microenvironment. Consequently, many promising preclinical findings have not been reproduced in human clinical trials. Organ-on-a-chip platforms can provide a solution to bridge this gap by offering human micro-(patho)physiological systems in which the immune system can be studied. This review provides an overview of the existing immune-organs-on-a-chip platforms, with a special emphasis on interorgan communication. In addition, future challenges to develop a comprehensive immune system-on-chip model are discussed.

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Section: State-of-the-art Immune-system-on-a-chip Modelsmentioning

confidence: 99%

Section: Limitations and Future Perspectivesmentioning

confidence: 99%

Immune Organs and Immune Cells on a Chip: An Overview of Biomedical Applications

et al. 2020

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“…[ 219,254,305,460–462 ] These include the role of shear stress on T cell‐dendritic cell trafficking, tumor‐dendritic cell communication, diffusional and perfusional transport dynamics between blood and lymphatic vasculature through the interstitial matrix, IF‐guided tumor cell migration, lymphatic morphogenesis and immune organoid development. [ 219,305,460,462–464 ] These studies aim to shed light on the various interstitial forces and associated biochemical signaling mechanisms that drive various pathologies including lymphedema, inflammation, and tumor cell dissemination.…”

Section: Modeling Vascular Mechanopathology In Vascularized Microphysmentioning

confidence: 99%

Biofabrication Strategies and Engineered In Vitro Systems for Vascular Mechanobiology

Pradhan

Banda

Farino

et al. 2020

Adv Healthcare Materials

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The vascular system is integral for maintaining organ‐specific functions and homeostasis. Dysregulation in vascular architecture and function can lead to various chronic or acute disorders. Investigation of the role of the vascular system in health and disease has been accelerated through the development of tissue‐engineered constructs and microphysiological on‐chip platforms. These in vitro systems permit studies of biochemical regulation of vascular networks and parenchymal tissue and provide mechanistic insights into the biophysical and hemodynamic forces acting in organ‐specific niches. Detailed understanding of these forces and the mechanotransductory pathways involved is necessary to develop preventative and therapeutic strategies targeting the vascular system. This review describes vascular structure and function, the role of hemodynamic forces in maintaining vascular homeostasis, and measurement approaches for cell and tissue level mechanical properties influencing vascular phenomena. State‐of‐the‐art techniques for fabricating in vitro microvascular systems, with varying degrees of biological and engineering complexity, are summarized. Finally, the role of vascular mechanobiology in organ‐specific niches and pathophysiological states, and efforts to recapitulate these events using in vitro microphysiological systems, are explored. It is hoped that this review will help readers appreciate the important, but understudied, role of vascular‐parenchymal mechanotransduction in health and disease toward developing mechanotherapeutics for treatment strategies.

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“…Along these lines, one feature that impacts tumor–immune cell interactions that has been difficult to capture with conventional models is the role of fluid flow. To address this limitation, a multicompartment microfluidic chip was recently developed that continuously circulates a small volume of fluid between two tissue samples . In one setup, fluid passes across a tumor slice and subsequently, across a LN slice to mimic the natural process of signals leaving tumors and draining to LNs.…”

Section: Biomaterials Enable Studies At the Interface Of Immune Cellsmentioning

confidence: 99%

Biomaterials as Tools to Decode Immunity

Eppler¹,

Jewell

2019

Advanced Materials

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The immune system has remarkable capabilities to combat disease with exquisite selectivity. This feature has enabled vaccines that provide protection for decades and, more recently, advances in immunotherapies that can cure some cancers. Greater control over how immune signals are presented, delivered, and processed will help drive even more powerful options that are also safe. Such advances will be underpinned by new tools that probe how immune signals are integrated by immune cells and tissues. Biomaterials are valuable resources to support this goal, offering robust, tunable properties. The growing role of biomaterials as tools to dissect immune function in fundamental and translational contexts is highlighted. These technologies can serve as tools to understand the immune system across molecular, cellular, and tissue length scales. A common theme is exploiting biomaterial features to rationally direct how specific immune cells or organs encounter a signal. This precision strategy, enabled by distinct material properties, allows isolation of immunological parameters or processes in a way that is challenging with conventional approaches. The utility of these capabilities is demonstrated through examples in vaccines for infectious disease and cancer immunotherapy, as well as settings of immune regulation that include autoimmunity and transplantation.

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Two-way communication betweenex vivotissues on a microfluidic chip: application to tumor–lymph node interaction

Abstract: The first microfluidic device for co-culture of two tissue slices under continuous recirculating flow was used to model tumor-induced immunosuppression.

Cited by 79 publications

References 66 publications

Immune Organs and Immune Cells on a Chip: An Overview of Biomedical Applications

Immune Organs and Immune Cells on a Chip: An Overview of Biomedical Applications

Biofabrication Strategies and Engineered In Vitro Systems for Vascular Mechanobiology

Biomaterials as Tools to Decode Immunity

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