Tumour-on-a-chip: microfluidic models of tumour morphology, growth and microenvironment

Tsai, Hsieh-Fu; Trubelja, Alen; Shen, Amy Q.; Bao, Gang

doi:10.1098/rsif.2017.0137

Cited by 159 publications

(135 citation statements)

References 206 publications

(302 reference statements)

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“…Other than previously described microfluidic devices that focus on tissue infection and inflammation, another important application of organ-on-a-chip systems is to recapitulate cancer growth and monitor therapeutic responses [210,211]. In general, microfluidic models of blood vessel systems, such as tumor blood vessels, can be employed to assess nanocarrier function or screen drug candidates to seek out new opportunities in cancer treatments [212].…”

Section: More Microfluidic Systems and Their Applicationsmentioning

confidence: 99%

In vitro and ex vivo systems at the forefront of infection modeling and drug discovery

Shi

Wang

et al. 2019

Biomaterials

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A B S T R A C TBacterial infections and antibiotic resistant bacteria have become a growing problem over the past decade. As a result, the Centers for Disease Control predict more deaths resulting from microorganisms than all cancers combined by 2050. Currently, many traditional models used to study bacterial infections fail to precisely replicate the in vivo bacterial environment. These models often fail to incorporate fluid flow, bio-mechanical cues, intercellular interactions, host-bacteria interactions, and even the simple inclusion of relevant physiological proteins in culture media. As a result of these inadequate models, there is often a poor correlation between in vitro and in vivo assays, limiting therapeutic potential. Thus, the urgency to establish in vitro and ex vivo systems to investigate the mechanisms underlying bacterial infections and to discover new-age therapeutics against bacterial infections is dire. In this review, we present an update of current in vitro and ex vivo models that are comprehensively changing the landscape of traditional microbiology assays. Further, we provide a comparative analysis of previous research on various established organ-disease models. Lastly, we provide insight on future techniques that may more accurately test new formulations to meet the growing demand of antibiotic resistant bacterial infections. Lack of adequate model systemsCommonly, a variety of inconsistent, in vitro and in vivo models have been progressively utilized for antibiotic/drug development and pathophysiological studies. These systems range from simple in vitro models using microtiter plate assays and flow cells to more complex in https://doi.

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Section: More Microfluidic Systems and Their Applicationsmentioning

confidence: 99%

In vitro and ex vivo systems at the forefront of infection modeling and drug discovery

Shi

Wang

et al. 2019

Biomaterials

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“…Therefore, it is particularly important to understand and mimic the complexity of TME for investigations on cancer metastasis. In brief, TME, involved in the physiological ecosystem for modulating cellular function, proliferation, and fate, mainly consists of malignant cells, nontransformed cell types, nutrients, soluble factors, signaling molecules, and metabolic and ECM components ( Figure ) . Taking advantage of dynamic networks of chemokines, cytokines, growth factors, matrix remodeling, and inflammatory enzymes, malignant cells actively interact with surrounding nonmalignant cells and ECM .…”

Section: Microfluidic Platforms For Engineered Tumor Microenvironmentmentioning

confidence: 99%

“…The TME consists of dynamic tumor cell–stromal cell interactions, and biochemical and physical connects between tumor cells and neighboring ECM. Reproduced with permission . Copyright 2017, The Royal Society of Chemistry.…”

Section: Microfluidic Platforms For Engineered Tumor Microenvironmentmentioning

confidence: 99%

“…As the primary tumor grows rapidly, the associated vasculature cannot provide adequate oxygen and nutrients in time leading to hypoxic regions (hypoxia) in the tumor. In turn, the hypoxia in the tumor affects selection of tumor cell genotypes, metabolic adjustment into anaerobic glycolysis, prosurvival gene expressions, as well as EMT . Hence, hypoxia is usually considered as a mediator of cancer progression and therapeutic resistance .…”

Section: Microfluidic Platforms For Engineered Tumor Microenvironmentmentioning

confidence: 99%

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Recent Advances in Microfluidic Platforms Applied in Cancer Metastasis: Circulating Tumor Cells' (CTCs) Isolation and Tumor‐On‐A‐Chip

Lin

Luo

et al. 2019

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Cancer remains the leading cause of death worldwide despite the enormous efforts that are made in the development of cancer biology and anticancer therapeutic treatment. Furthermore, recent studies in oncology have focused on the complex cancer metastatic process as metastatic disease contributes to more than 90% of tumor‐related death. In the metastatic process, isolation and analysis of circulating tumor cells (CTCs) play a vital role in diagnosis and prognosis of cancer patients at an early stage. To obtain relevant information on cancer metastasis and progression from CTCs, reliable approaches are required for CTC detection and isolation. Additionally, experimental platforms mimicking the tumor microenvironment in vitro give a better understanding of the metastatic microenvironment and antimetastatic drugs' screening. With the advancement of microfabrication and rapid prototyping, microfluidic techniques are now increasingly being exploited to study cancer metastasis as they allow precise control of fluids in small volume and rapid sample processing at relatively low cost and with high sensitivity. Recent advancements in microfluidic platforms utilized in various methods for CTCs' isolation and tumor models recapitulating the metastatic microenvironment (tumor‐on‐a‐chip) are comprehensively reviewed. Future perspectives on microfluidics for cancer metastasis are proposed.

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“…Other studies have recently reported that the presence of EC in the microenvironment of the microfluidic device affect in the establishment and growth of MCTS. (Katt et al, ; Lv, Hu, Lu, Lu, & Xu, ; H. F. Tsai, Trubelja, Shen, & Bao, ; van Duinen et al, ). However, conventional MCTS generation methods still have limitations in fully mimicking in vivo tumor‐microenvironment interactions and tumor progression.…”

Section: Introductionmentioning

confidence: 99%

In vitro lung cancer multicellular tumor spheroid formation using a microfluidic device

Lee

Hong

Jung

et al. 2019

Biotech & Bioengineering

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The purpose of this study was to demonstrate self‐organizing in vitro multicellular tumor spheroid (MCTS) formation in a microfluidic system and to observe the behavior of MCTSs under controlled microenvironment. The employed microfluidic system was designed for simple and effective formation of MCTSs by generating nutrient and oxygen gradients. The MCTSs were composed of cancer cells, vascular endothelial cells, and type I collagen matrix to mimic the in vivo tumor microenvironment (TME). Cell culture medium was perfused to the microfluidic device loaded with MCTSs by a passive fluidic pump at a constant flow rate. The dose response to an MMPs inhibitor was investigated to demonstrate the effects of biochemical substances. The result of long‐term stability of MCTSs revealed that continuous perfusion of cell culture medium is one of the major factors for the successful MCTS formation. A continuous flow of cell culture medium in the in vitro TME greatly affected both the proliferation of cancer cells in the micro‐wells and the sustainability of the endothelial cell‐layer integrity in the lumen of microfluidic channels. Addition of MMP inhibitor to the cell culture medium improved the stability of the collagen matrix by preventing the detachment and shrinkage of the collagen matrix surrounding the MCTSs. In summary, the present constant flow assisted microfluidic system is highly advantageous for long‐term observation of the MCTS generation, tumorous tissue formation process and drug responses. MCTS formation in a microfluidic system may serve as a potent tool for studying drug screening, tumorigenesis and metastasis.

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Tumour-on-a-chip: microfluidic models of tumour morphology, growth and microenvironment

Cited by 159 publications

References 206 publications

In vitro and ex vivo systems at the forefront of infection modeling and drug discovery

In vitro and ex vivo systems at the forefront of infection modeling and drug discovery

Recent Advances in Microfluidic Platforms Applied in Cancer Metastasis: Circulating Tumor Cells' (CTCs) Isolation and Tumor‐On‐A‐Chip

In vitro lung cancer multicellular tumor spheroid formation using a microfluidic device

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