On-chip human microvasculature assay for visualization and quantification of tumor cell extravasation dynamics
TLDR
In this article, the authors describe an in vitro model of the human microcirculation with the potential to recapitulate discrete steps of early metastatic seeding, including arrest, transendothelial migration and early micrometastases formation.Abstract:
Distant metastasis, which results in >90% of cancer-related deaths, is enabled by hematogenous dissemination of tumor cells via the circulation. This requires the completion of a sequence of complex steps including transit, initial arrest, extravasation, survival and proliferation. Increased understanding of the cellular and molecular players enabling each of these steps is key to uncovering new opportunities for therapeutic intervention during early metastatic dissemination. As a protocol extension, this article describes an adaptation to our existing protocol describing a microfluidic platform that offers additional applications. This protocol describes an in vitro model of the human microcirculation with the potential to recapitulate discrete steps of early metastatic seeding, including arrest, transendothelial migration and early micrometastases formation. The microdevice features self-organized human microvascular networks formed over 4-5 d, after which the tumor can be perfused and extravasation events are easily tracked over 72 h via standard confocal microscopy. Contrary to most in vivo and in vitro extravasation assays, robust and rapid scoring of extravascular cells, combined with high-resolution imaging, can be easily achieved because of the confinement of the vascular network to one plane close to the surface of the device. This renders extravascular cells clearly distinct and allows tumor cells of interest to be identified quickly as compared with those in thick tissues. The ability to generate large numbers of devices (∼36) per experiment further allows for highly parametric studies, which are required when testing multiple genetic or pharmacological perturbations. This is coupled with the capability for live tracking of single-cell extravasation events, allowing both tumor and endothelial morphological dynamics to be observed in high detail with a moderate number of data points.read more
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Modelling cancer in microfluidic human organs-on-chips.
Alexandra Sontheimer-Phelps,Bryan Hassell,Bryan Hassell,Donald E. Ingber,Donald E. Ingber,Donald E. Ingber +5 more
TL;DR: This Review outlines how recent developments in microfluidic cell culture technology have led to the generation of human organs-on-chips that are now being used to model cancer cell behaviour within human-relevant tissue and organ microenvironments in vitro.
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3D self-organized microvascular model of the human blood-brain barrier with endothelial cells, pericytes and astrocytes
Marco Campisi,Yoojin Shin,Tatsuya Osaki,Cynthia Hajal,Valeria Chiono,Roger D. Kamm,Roger D. Kamm +6 more
TL;DR: A robust and physiologically relevant BBB microvascular model offers an innovative and valuable platform for drug discovery to predict neuro-therapeutic transport efficacy in pre-clinical applications as well as recapitulate patient-specific and pathological neurovascular functions in neurodegenerative disease.
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Organoids-on-a-chip.
TL;DR: This Review explores organ-on-a-chip technology as a platform to fulfill this need for innovative engineering approaches for the production, control, and analysis of organoids and their microenvironment and examines how this technology may be leveraged to address major technical challenges in organoid research.
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Interconnected Microphysiological Systems for Quantitative Biology and Pharmacology Studies
Collin Edington,Wen Li Kelly Chen,Emily Geishecker,Timothy Kassis,Luis R. Soenksen,Brij Bhushan,Duncan Freake,Jared Kirschner,Christian Maass,Nikolaos Tsamandouras,Jorge Valdez,Christi D. Cook,Thomas Gerard Parent,Stephen Snyder,Jiajie Yu,Emily Suter,Michael Shockley,Jason Velazquez,Jeremy J. Velazquez,Linda Stockdale,Julia P. Papps,Iris Lee,Nicholas Vann,Mario E. Gamboa,Matthew E. LaBarge,Zhe Zhong,Xin Wang,Laurie A. Boyer,Douglas A. Lauffenburger,Catherine Communal,Steven R. Tannenbaum,Cynthia L. Stokes,David Hughes,Gaurav Rohatgi,David L. Trumper,Murat Cirit,Linda G. Griffith +36 more
TL;DR: An approach to co-culture multiple different MPSs linked together physiologically on re-useable, open-system microfluidic platforms that are compatible with the quantitative study of a range of compounds, including lipophilic drugs is reported.
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From Shape to Function: The Next Step in Bioprinting
TL;DR: The recent material and technological advances since the introduction of the biofabrication window are briefly summarized, i.e., approaches how to generate shape, to then focus the discussion on how to acquire the biological function within this context.
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