Gels for Live Analysis of Compartmentalized Environments (GLAnCE): A tissue model to probe tumour phenotypes at tumour-stroma interfaces

D’Arcangelo, Elisa; Wu, Nila C.; Chen, Tianhao; Shahaj, Andi; Cadavid, Jose L.; Huang, Leo; Ailles, Laurie; McGuigan, Alison P.

doi:10.1016/j.biomaterials.2019.119572

Cited by 12 publications

(10 citation statements)

References 63 publications

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“…Immunostaining of Organoids: To assess PDO morphology and phenotype in Matrigel, PDOs were cultured in Matrigel gels contained in the GLAnCE platform [62] to prevent cell loss during fixation. To assess ODC maturity and polarization in the cellulose paper scaffold, discs were seeded with ODCs as described above.…”

Section: Ef5-based Analysis Of Oxygen Gradients In Tracer2mentioning

confidence: 99%

An Engineered Patient‐Derived Tumor Organoid Model That Can Be Disassembled to Study Cellular Responses in a Graded 3D Microenvironment

Landon-Brace

Cadavid

Latour

et al. 2021

Adv Funct Materials

Self Cite

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Patient-derived organoids (PDOs) are emerging as powerful models to capture the genetic heterogeneity of human tumors. However, the self-assembling nature of PDOs limits their use in studies of the impact of microenvironmental heterogeneity on tumor cell function. Here, a paper-based model, the Tissue Roll for Analysis of Cellular Environment and Response (TRACER) is adapted, using patterned polymer infiltration, to enable controlled assembly and disassembly of organoid structures to study the impact of both genetic and microenvironmental heterogeneity on tumor cell behavior. In the adapted platform (TRACER2), pancreatic cancer PDOs establish oxygen gradients across the tissue and in response exhibit graded cell viability, proliferation, hypoxiaresponse gene transcription, and response to gemcitabine therapy. Further, PDOs retrieved from the hypoxic regions of the TRACER2 cultures show graded transcriptional changes in immunosuppression-related genes and upon co-culture, after TRACER2 disassembly, induce graded functional changes in Jurkat cells and macrophage cells. Therefore, TRACER2 offers a novel platform to dissect the effects of microenvironmental parameters on tumor cell function.

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Section: Ef5-based Analysis Of Oxygen Gradients In Tracer2mentioning

confidence: 99%

An Engineered Patient‐Derived Tumor Organoid Model That Can Be Disassembled to Study Cellular Responses in a Graded 3D Microenvironment

Landon-Brace

Cadavid

Latour

et al. 2021

Adv Funct Materials

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“…Further, hydrogel plugs do not facilitate longitudinal in situ imaging of organoid phenotype due to the curved surface and high gel thickness associated with the hydrogel meniscus. The ability to perform longitudinal imaging of tumour cell cultures is important as we [35], [36] and others [25], [71], have shown the benefits of using this approach to provide a deeper understanding of organoid response to therapy. Here, we described the use of a thin paper scaffold to create supported hydrogel microtissues without a meniscus that enable the culture and long-term imaging of tumour organoids for analysis of drug response.…”

Section: Discussionmentioning

confidence: 99%

“…A need exists therefore for a 3D hydrogel culture platform compatible with PDO cultures, with the potential for high-throughput manufacturing and that facilitates high-throughput phenotypic (likely image-based) analysis which has been shown to acquire richer information about cellular behaviour [34]. In previous work, we reported a 3D in vitro model, Gels for Live Analysis of Compartmentalized Environments (GLAnCE), in which cells are suspended in a thin layer of gel to enable non-destructive data acquisition over time using widefield microscopy, rather than time-laborious and data-intensive confocal microscopy [35], [36]. While GLAnCE addresses the need for a 3D culture platform that enables ease-of-imaging, the throughput possible with GLAnCE is limited because it requires multiple assembly steps (i.e., pre-and post-seeding) and would be challenging to integrate with automated robotic manufacturing.…”

Section: Introductionmentioning

confidence: 99%

An off-the-shelf multi-well scaffold-supported platform for tumour organoid-based tissues

Li¹,

Wu²,

Cao³

et al. 2022

Preprint

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Complex 3D bioengineered tumour models provide the opportunity to better capture the heterogeneity of patient tumours. Patient-derived organoids are emerging as a useful tool to study tumour heterogeneity and variation in patient responses. Organoid cultures typically require a 3D microenvironment that can be manufactured easily to facilitate screening. Here we set out to create a high-throughput, "off-the-shelf" platform which permits the generation of organoid- containing microtissues for standard phenotypic bioassays and image-based readings. To achieve this, we developed the Scaffold-supported Platform for Organoid-based Tissues (SPOT) platform. SPOT is a 3D gel-embedded in vitro platform that can be produced in a 96- or 384-well plate format and enables the generation of flat, thin and dimensionally-defined microgels. SPOT has high potential for adoption due to its reproducible manufacturing methodology, compatibility with existing instrumentation, and reduced within-sample and between-sample variation, which can pose challenges to both data analysis and interpretation. Using SPOT we generate cultures from patient derived pancreatic ductal adenocarcinoma organoids and assess the cellular response to standard-of-care chemotherapeutic compounds, demonstrating our platform's usability for drug screening. We envision 96/384-SPOT will provide a useful tool to assess drug sensitivity of patient-derived organoids and easily integrate into the drug discovery pipeline.

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“…This plate of channels is compatible with standard widefield fluorescence imaging, and similarly to TRACER, cells can be harvested from the collagen slabs after imaging for further downstream experiments. In their study, images of fluorescently labelled cells showed morphological changes suggestive of an invasive phenotype in tumor cells at the CAF–tumor interface, as well as increased migration outwards from the interface [ 84 ].…”

Section: Compartmentalizing the Tumormentioning

confidence: 99%

Modeling the Role of Cancer-Associated Fibroblasts in Tumor Cell Invasion

Poon

Ailles

2022

Cancers

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The major cause of cancer-related deaths can be attributed to the metastatic spread of tumor cells—a dynamic and complex multi-step process beginning with tumor cells acquiring an invasive phenotype to allow them to travel through the blood and lymphatic vessels to ultimately seed at a secondary site. Over the years, various in vitro models have been used to characterize specific steps in the cascade to collectively begin providing a clearer picture of the puzzle of metastasis. With the discovery of the TME’s supporting role in activating tumor cell invasion and metastasis, these models have evolved in parallel to accommodate features of the TME and to observe its interactions with tumor cells. In particular, CAFs that reside in reactive tumor stroma have been shown to play a substantial pro-invasive role through their matrix-modifying functions; accordingly, this warranted further investigation with the development and use of invasion assays that could include these stromal cells. This review explores the growing toolbox of assays used to study tumor cell invasion, from the simple beginnings of a tumor cell and extracellular matrix set-up to the advent of models that aim to more closely recapitulate the interplay between tumor cells, CAFs and the extracellular matrix. These models will prove to be invaluable tools to help tease out the intricacies of tumor cell invasion.

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Gels for Live Analysis of Compartmentalized Environments (GLAnCE): A tissue model to probe tumour phenotypes at tumour-stroma interfaces

Cited by 12 publications

References 63 publications

An Engineered Patient‐Derived Tumor Organoid Model That Can Be Disassembled to Study Cellular Responses in a Graded 3D Microenvironment

An Engineered Patient‐Derived Tumor Organoid Model That Can Be Disassembled to Study Cellular Responses in a Graded 3D Microenvironment

An off-the-shelf multi-well scaffold-supported platform for tumour organoid-based tissues

Modeling the Role of Cancer-Associated Fibroblasts in Tumor Cell Invasion

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