Recent advances in vascularized tumor-on-a-chip

Huang, Christina Bao Xian; Tu, Ting‐Yuan

doi:10.3389/fonc.2023.1150332

Cited by 8 publications

(5 citation statements)

References 102 publications

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“…Secondary metastatic sites can include the mesentery, the liver, the omentum or the peritoneum ( Micek et al, 2020 ). Metastasis to the peritoneum is accompanied by an abnormal accumulation of ascitic fluid rich in cells and proteins, and this is associated with a poor median patient survival ( Finkernagel et al, 2019 ; Huang and Tu, 2023 ). A critical step in the progression of ovarian cancer metastasis is the epithelial-to-mesenchymal transition (EMT), which is characterized by the loss of E-cadherin, cytoskeletal remodeling and changes in proliferation, motility and apoptosis ( Ahmed et al, 2007 ; Moreno-Bueno et al, 2009 ; Datta et al, 2021 ).…”

Section: Current Microphysiological Systems Of ‘Cold’ Tumorsmentioning

confidence: 99%

Microphysiological systems as models for immunologically ‘cold’ tumors

Gaebler,

Hachey,

Hughes

2024

Front. Cell Dev. Biol.

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The tumor microenvironment (TME) is a diverse milieu of cells including cancerous and non-cancerous cells such as fibroblasts, pericytes, endothelial cells and immune cells. The intricate cellular interactions within the TME hold a central role in shaping the dynamics of cancer progression, influencing pivotal aspects such as tumor initiation, growth, invasion, response to therapeutic interventions, and the emergence of drug resistance. In immunologically ‘cold’ tumors, the TME is marked by a scarcity of infiltrating immune cells, limited antigen presentation in the absence of potent immune-stimulating signals, and an abundance of immunosuppressive factors. While strategies targeting the TME as a therapeutic avenue in ‘cold’ tumors have emerged, there is a pressing need for novel approaches that faithfully replicate the complex cellular and non-cellular interactions in order to develop targeted therapies that can effectively stimulate immune responses and improve therapeutic outcomes in patients. Microfluidic devices offer distinct advantages over traditional in vitro 3D co-culture models and in vivo animal models, as they better recapitulate key characteristics of the TME and allow for precise, controlled insights into the dynamic interplay between various immune, stromal and cancerous cell types at any timepoint. This review aims to underscore the pivotal role of microfluidic systems in advancing our understanding of the TME and presents current microfluidic model systems that aim to dissect tumor-stromal, tumor-immune and immune-stromal cellular interactions in various ‘cold’ tumors. Understanding the intricacies of the TME in ‘cold’ tumors is crucial for devising effective targeted therapies to reinvigorate immune responses and overcome the challenges of current immunotherapy approaches.

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Section: Current Microphysiological Systems Of ‘Cold’ Tumorsmentioning

confidence: 99%

Microphysiological systems as models for immunologically ‘cold’ tumors

Gaebler,

Hachey,

Hughes

2024

Front. Cell Dev. Biol.

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“…Factors such as shear stress, oxygen concentration, and fluid flow rate are critical in creating a vasculature‐on‐a‐chip model. [ 14,16,40,46,58,72,83,118,166–168,171 ] They must be carefully controlled to accurately represent the in vivo environment. Overall, the development of vasculature‐on‐a‐chip technology has opened up exciting new possibilities for in vitro modeling of vascular diseases and drug screening and will undoubtedly continue to play a significant role in medical research in the future.…”

Section: Current Challenges and New Directions In The Vtoc Advancemen...mentioning

confidence: 99%

“…[ 169,170 ] Vasculature disease models have been created using vasculature‐on‐a‐chip technology, enabling researchers to investigate issues with the vessel wall, such as endothelial dysfunction, and the role of blood vessels in adjacent tissue and organ function abnormalities, such as tumors. [ 17,42,43,130,158,162,163,165,166,170–172 ]…”

Section: Current Challenges and New Directions In The Vtoc Advancemen...mentioning

confidence: 99%

An Overview of Advancements and Technologies in Vascularization Strategies for Tumor‐On‐A‐Chip Models

Parihar,

Sunildutt,

Rahim

et al. 2024

Advanced Therapeutics

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Vascularized tumor on a chip (VToC) entails emulating intricate microvascular networks like those observed in tumors through microfluidic devices, which are meticulously designed to offer a faithful representation of cancer in vitro, exploration of tumor biology, evaluation of drug efficacy, and anticipation of patient responses to therapies. Compared to conventional ones, VToC systems hold advantages by creating a milieu where physiological conditions for investigating tumor‐host interactions are pivotal in tumor advancement/therapy resilience. Nevertheless, VToC models confront limitations encompassing vascular network replication, biological fidelity, mechanical/chemical integrity, and intricacies of architectural design. Thus, drawbacks inherent to prevailing VToC models' intricacies, attributes, and vascular network establishment are imperative. This systematic review focuses on the recent advancements, technologies explored for incorporating VToC models, & vascularization approaches for investigation, and factors/parameters affecting complex tumor microenvironments in VToC models, along with the futuristic approach for the design strategies, fabrication techniques, understanding of vascular network, also VToC models with spheroid. A comprehensive analysis of VToC based on their limitations for a practical approach highlights the promising strategies for possible applications. This review will be essential regarding a complete overview of VToC models and the future direction toward developing efficient VToC models compared to the state‐of‐the‐art VToC.This article is protected by copyright. All rights reserved

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“…Their preclinical relevance and reliability have been assessed and confirmed [ 7 , 8 ], laying the groundwork for potential scalability within the industry. Besides, these in vitro models include dynamic interactions between the different compartments, most often by the perfusion of the liquid environment, to constitute a vascularized tumor model (VTM) [ 9 – 11 ]. Indeed, the tumor vasculature plays a pivotal role in essential processes such as immune response, drug delivery [ 12 ], or metastasis mechanisms (notably through its influence on the epithelial-mesenchymal plasticity (EMP) [ 13 ]).…”

Section: Introductionmentioning

confidence: 99%

Vascularized tumor models for the evaluation of drug delivery systems: a paradigm shift

Lopez-Vince,

Wilhelm,

Simon-Yarza

2024

Drug Deliv. and Transl. Res.

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As the conversion rate of preclinical studies for cancer treatment is low, user-friendly models that mimic the pathological microenvironment and drug intake with high throughput are scarce. Animal models are key, but an alternative to reduce their use would be valuable. Vascularized tumor-on-chip models combine great versatility with scalable throughput and are easy to use. Several strategies to integrate both tumor and vascular compartments have been developed, but few have been used to assess drug delivery. Permeability, intra/extravasation, and free drug circulation are often evaluated, but imperfectly recapitulate the processes at stake. Indeed, tumor targeting and chemoresistance bypass must be investigated to design promising cancer therapeutics. In vitro models that would help the development of drug delivery systems (DDS) are thus needed. They would allow selecting good candidates before animal studies based on rational criteria such as drug accumulation, diffusion in the tumor, and potency, as well as absence of side damage. In this review, we focus on vascularized tumor models. First, we detail their fabrication, and especially the materials, cell types, and coculture used. Then, the different strategies of vascularization are described along with their classical applications in intra/extravasation or free drug assessment. Finally, current trends in DDS for cancer are discussed with an overview of the current efforts in the domain. Graphical Abstract

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Recent advances in vascularized tumor-on-a-chip

Cited by 8 publications

References 102 publications

Microphysiological systems as models for immunologically ‘cold’ tumors

Microphysiological systems as models for immunologically ‘cold’ tumors

An Overview of Advancements and Technologies in Vascularization Strategies for Tumor‐On‐A‐Chip Models

Vascularized tumor models for the evaluation of drug delivery systems: a paradigm shift

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