Modeling 3D Human Tumor Lymphatic Vessel Network Using High‐Throughput Platform

Lee, Somin; Kang, Habin; Park, Dohyun; Yu, James; Koh, Seong Ho; Cho, Duck; Kim, Da‐Hyun; Kang, Kyungsik; Jeon, Noo Li

doi:10.1002/adbi.202000195

Cited by 16 publications

(22 citation statements)

References 98 publications

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“…In the context of cancer immunotherapy, researchers have started utilizing OoCs to investigate cancer cell-immune cell interactions in 3D environments 308 . There are also efforts to form lymphatic vessels within OoCs to study how cancer cells remodel the tumour microenvironment 309 . Recent studies also highlight the roles of endothelial-immune cell or pathogen crosstalk in modulating immune response 310,311 .…”

Section: Biological Applicationsmentioning

confidence: 99%

A guide to the organ-on-a-chip

Leung

Haan

Ronaldson-Bouchard

et al. 2022

Nat Rev Methods Primers

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276

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The organ-on-a-chip (OoC) is an intriguing scientific and technological development in which biology is coupled with microtechnology 1,2 to mimic key aspects of human physiology. The chip takes the form of a microfluidic device containing networks of hair-fine microchannels for guiding and manipulating minute volumes (picolitres up to millilitres) of solution [3][4][5] . The organ is a more relatable term that refers to the miniature tissues grown and residing in the microfluidic chips, which can recapitulate one or more tissue-specific functions. Although they are much simpler than native tissues and organs, scientists have discovered that these systems can often serve as effective mimics of human physiology and disease. OoCs comprise advanced in vitro technology that enables experimentation with biological cells and tissues outside the body. This is achieved by containing them inside vessels conditioned to sustain a reasonable semblance of the in vivo environment, from a biochemical and physical point of view. Working on the microscale lends a unique opportunity to attain a higher level of control over the microenvironment that ensures tissue life support, as well as a means to directly observe cell and tissue behaviour.The OoC is a relatively recent addition to the toolbox of model biological systems available to life science researchers to probe aspects of human pathophysiology and disease. These systems cover a spectrum of physiological relevance, with 2D cell cultures the least relevant, followed in increasing order by 3D cell cultures, organoids and OoCs. Unsurprisingly, the use of model organisms such as mice and Drosophila physiologically exceeds engineered tissue approaches 6,7 . While biological complexity increases with physiological relevance in model organisms, this unfortunately leads to increased experimental difficulty. In vivo physiological processes are, in many ways, the least accessible to direct investigation in mice, humans and other mammals, despite significant advances in in vivo imaging. However, 2D and 3D cell cultures, such as spheroids and stem cell-derived organoids, sacrifice some aspects of in vivo relevance to facilitate experimentation. The OoC may be regarded as a bridging technology, offering the ability to work with complex cell cultures, while providing better engineered microenvironments to maximize the model.Following on from early concepts, including animal-on-a-chip 8 , body-on-a-chip 9 and breathing lung-on-a-chip 10 , research in the OoC and microphysiological systems fields has grown exponentially; evidenced by numerous excellent reviews published recently 1,2,11 . Recognition of OoC technology now extends far beyond university laboratories, driven by a need to better understand the human physiology underlying health and disease, and to find new approaches to improve the human condition. The World Economic Forum, for instance, selected the OoC as one of the top ten emerging technologies in 2016 (ref. 12

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Section: Biological Applicationsmentioning

confidence: 99%

A guide to the organ-on-a-chip

Leung

Haan

Ronaldson-Bouchard

et al. 2022

Nat Rev Methods Primers

Self Cite

509

276

View full text Add to dashboard Cite

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“…Increased understanding of the role of lymphatic vessels in development, homeostasis and disease will be important for engineering vascular networks. Emerging work is already looking towards building human lymphatic vessel networks using both technological and self-assembly-based approaches 162 , 163 .…”

Section: Emerging Frontiersmentioning

confidence: 99%

Engineering the multiscale complexity of vascular networks

et al. 2022

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The survival of vertebrate organisms depends on highly regulated delivery of oxygen and nutrients through vascular networks that pervade nearly all tissues in the body. Dysregulation of these vascular networks is implicated in many common human diseases such as hypertension, coronary artery disease, diabetes and cancer. Therefore, engineers have sought to create vascular networks within engineered tissues for applications such as regenerative therapies, human disease modelling and pharmacological testing. Yet engineering vascular networks has historically remained difficult, owing to both incomplete understanding of vascular structure and technical limitations for vascular fabrication. This Review highlights the materials advances that have enabled transformative progress in vascular engineering by ushering in new tools for both visualizing and building vasculature. New methods such as bioprinting, organoids and microfluidic systems are discussed, which have enabled the fabrication of 3D vascular topologies at a cellular scale with lumen perfusion. These approaches to vascular engineering are categorized into technology-driven and nature-driven approaches. Finally, the remaining knowledge gaps, emerging frontiers and opportunities for this field are highlighted, including the steps required to replicate the multiscale complexity of vascular networks found in nature.

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“…Once the device design and fabrication steps are optimized for injection modeling, the entire production process becomes considerably simpler and faster than conventional soft lithography. An injection-molded plastic array platform mimicking the 3D tumor lymphatic vascular network has shown great potential for high-throughput drug testing [ 112 ]. However, the range of materials that can be used for injection molding is limited [ 113 ].…”

Section: Advanced Engineering Technology In Organs-on-chipsmentioning

confidence: 99%

Design and engineering of organ-on-a-chip

2023

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Organ-on-a-chip (OOC) is an emerging interdisciplinary technology that reconstitutes the structure, function, and physiology of human tissues as an alternative to conventional preclinical models for drug screening. Over the last decade, substantial progress has been made in mimicking tissue- and organ-level functions on chips through technical advances in biomaterials, stem cell engineering, microengineering, and microfluidic technologies. Structural and engineering constituents, as well as biological components, are critical factors to be considered to reconstitute the tissue function and microenvironment on chips. In this review, we highlight critical engineering technologies for reconstructing the tissue microarchitecture and dynamic spatiotemporal microenvironment in OOCs. We review the technological advances in the field of OOCs for a range of applications, including systemic analysis tools that can be integrated with OOCs, multiorgan-on-chips, and large-scale manufacturing. We then discuss the challenges and future directions for the development of advanced end-user-friendly OOC systems for a wide range of applications.

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Modeling 3D Human Tumor Lymphatic Vessel Network Using High‐Throughput Platform

Cited by 16 publications

References 98 publications

A guide to the organ-on-a-chip

A guide to the organ-on-a-chip

Engineering the multiscale complexity of vascular networks

Design and engineering of organ-on-a-chip

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