Enabling perfusion through multicellular tumor spheroids promoting lumenization in a vascularized cancer model

Park, Joonha; Kim, Seung Gyu; Hong, Ji‐Man; Jeon, Jessie S.

doi:10.1039/d2lc00597b

Cited by 19 publications

(15 citation statements)

References 81 publications

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“…Park et al. ( 31 ) demonstrate the use of tri-culture spheroid comprising tumor cells, ECs, and fibroblasts. The tri-culture spheroid has a more robust intratumoral vasculature and connects better with the external microvasculature network.…”

Section: Vascularization Strategiesmentioning

confidence: 99%

Recent advances in vascularized tumor-on-a-chip

Huang

2023

Front. Oncol.

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The vasculature plays a critical role in cancer progression and metastasis, representing a pivotal aspect in the creation of cancer models. In recent years, the emergence of organ-on-a-chip technology has proven to be a robust tool, capable of replicating in vivo conditions with exceptional spatiotemporal resolution, making it a significant asset in cancer research. This review delves into the latest developments in 3D microfluidic vascularized tumor models and their applications in vitro, focusing on heterotypic cellular interactions, the mechanisms of metastasis, and therapeutic screening. Additionally, the review examines the benefits and drawbacks of these models, as well as the future prospects for their advancement.

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Section: Vascularization Strategiesmentioning

confidence: 99%

Recent advances in vascularized tumor-on-a-chip

Huang

2023

Front. Oncol.

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“…Owing to the independent compartments in microfluidics, various parameters, such as mechanical forces, tissue interface orientation, cell types and localization, and biochemical gradients, can be precisely controlled. Microfluidics can introduce different cell types and circulating systems (such as blood or lymphatic vessels) into the 3D structure, thereby providing an ideal platform for TME or cancer-immunity cycle (CIC) research, as well as for drug testing and discovery [113][114][115][116]. Moreover, microfluidic devices require a very small volume of samples and reagents for analysis; therefore, they have great potential for high-throughput screening [117,118].…”

Section: Vessel-based Dynamic 3d Modelsmentioning

confidence: 99%

“…Microfluidic chips can be used to evaluate antimetastatic therapies and investigate the mechanisms underlying vasculature-driven invasive tumor phenotypes.Bai et al [119] embedded bladder cancer cell aggregates in a collagen scaffold adjacent to an endothelial cell channel to screen therapeutic epithelial-mesenchymal transition blocking agents. The efficacy of each drug was evaluated based on its Reproduced from [116] with permission from the Royal Society of Chemistry. (iii) Fluorescence image showing CTL clustering on the spheroid during first fragmentation event.…”

Section: Vessel-based Dynamic 3d Modelsmentioning

confidence: 99%

“…The combination of a dynamic 3D culture and perfusion of cells or agents can be used to recapitulate the multi-niche interaction and drug evaluation. (ii) Fluorescence image of perfusable vascularized tumors (day 4).Reproduced from[116] with permission from the Royal Society of Chemistry. (iii) Fluorescence image showing CTL clustering on the spheroid during first fragmentation event.…”

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confidence: 99%

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Reconstruction of tumor microenvironment via in vitro three-dimensional models

Zhou

Pang

et al. 2023

Biofabrication

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Recent advances in tumor microenvironment (TME) modeling as well as its applications to cancer therapy has brought various dramatical changes in multiple malignancies management. Understanding the mechanisms of response and resistance to cancer therapy requires a clear elucidation of the intricate interactions between TME cells, the surrounding stroma, and distant affected tissues or organs. To address this demand, various 3D cell culture techniques have been developed in order to recapitulate and understand cancer biology over the past decade. This review summarizes some saliant progresses in in vitro 3D TME modeling, including the cell-based, matrix-based, and vessel-based dynamic 3D modeling techniques and their applications in investigating tumor-stroma interactions and responses to cancer therapies. The review also discusses the limitations of current TME modelling approaches and proposes some new thoughts on the construction of more clinically relevant models.

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“…With the continuous development of microfabrication technology, microfluidic tumor–vessel chips not only help to precisely arrange the spatial distribution of cellular components in vitro but can also apply biomechanical and biochemical stimuli, including blood flow and growth factor gradient, thereby reproducing the interaction between the heterotypic tumor and TME with high fidelity. − For example, Haase et al reported an on-chip 3D-vascularized tumor model for drug examination in a TME within a large bed of perfusable vasculature. , They demonstrated that the dose-dependent effect of anticancer drugs on tumor activity was significantly affected by the form of vascular infusion administration. Meanwhile, great strides have also been made in the field of biomaterials. , As a representative biomaterial, GelMA has been widely used in the regenerative medicine field for 3D cell culture. , Various organ models have been successfully established in GelMA, which demonstrate its good biocompatibility. ,, Antunes et al reported an in-air production of tumor spheroid-laden GelMA microgel to expedite drug screening, where GelMA was involved as tumor–ECM .…”

Section: Introductionmentioning

confidence: 99%

Microfluidic Droplet-Assisted Fabrication of Vessel-Supported Tumors for Preclinical Drug Discovery

Zhao

Zhou

et al. 2023

ACS Appl. Mater. Interfaces

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High-fidelity in vitro tumor models are important for preclinical drug discovery processes. Currently, the most commonly used model for in vitro drug testing remains the two-dimensional (2D) cell monolayer. However, the natural in vivo tumor microenvironment (TME) consists of extracellular matrix (ECM), supporting stromal cells and vasculature. They not only participate in the progression of tumors but also hinder drug delivery and effectiveness on tumor cells. Here, we report an integrated engineering system to generate vesselsupported tumors for preclinical drug screening. First, gelatin-methacryloyl (GelMA) hydrogel was selected to mimic tumor extracellular matrix (ECM). HCT-116 tumor cells were encapsulated into individual micro-GelMA beads with microfluidic droplet technique to mimic tumor−ECM interactions in vitro. Then, normal human lung fibroblasts were mingled with tumor cells to imitate the tumor−stromal interaction. The tumor cells and fibroblasts reconstituted in the individual GelMA microbead and formed a biomimetic heterotypic tumor model with a core−shell structure. Next, the cell-laden beads were consociated into a functional on-chip vessel network platform to restore the tumor−tumor microenvironment (TME) interaction. Afterward, the anticancer drug paclitaxel was tested on the individual and vessel-supported tumor models. It was demonstrated that the blood vessel-associated TME conferred significant additional drug resistance in the drug screening experiment. The reported system is expected to enable the large-scale fabrication of vessel-supported heterotypic tumor models of various cellular compositions. It is believed to be promising for the large-scale fabrication of biomimetic in vitro tumor models and may be valuable for improving the efficiency of preclinical drug discovery processes.

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Enabling perfusion through multicellular tumor spheroids promoting lumenization in a vascularized cancer model

Abstract: Tumor is composed of heterogeneous cell population, which is known as tumor stroma. In particular, blood vessels have an indispensable role in the tumor microenvironment acting as a key player...

Cited by 19 publications

References 81 publications

Recent advances in vascularized tumor-on-a-chip

Recent advances in vascularized tumor-on-a-chip

Reconstruction of tumor microenvironment via in vitro three-dimensional models

Microfluidic Droplet-Assisted Fabrication of Vessel-Supported Tumors for Preclinical Drug Discovery

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