The Applications and Challenges of the Development of In Vitro Tumor Microenvironment Chips

Johnson, Annika; Reimer, Samuel; Childres, Ryan; Cupp, Grace; Kohs, Tia C L; McCarty, Owen J. T.; Kang, Young Bok Abraham

doi:10.1007/s12195-022-00755-7

Cited by 9 publications

(5 citation statements)

References 123 publications

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“…However, key challenges remain for the successful implementation of such devices in vitro. 165,166 These challenges stem from the high variability in the fabrication methods of each device that reduces the reproduction and standardization of culturing cells on microchips. Also, to better recapitulate the in vivo microenvironment, multiple cell lines should be introduced on a microchip platform either seeded as a monolayer or growing as spheroids.…”

Section: Conclusive Remarks and Remaining Challengesmentioning

confidence: 99%

Toward innovative approaches for exploring the mechanically regulated tumor-immune microenvironment

Kalli,

Stylianopoulos

2024

APL Bioengineering

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Within the complex tumor microenvironment, cells experience mechanical cues—such as extracellular matrix stiffening and elevation of solid stress, interstitial fluid pressure, and fluid shear stress—that significantly impact cancer cell behavior and immune responses. Recognizing the significance of these mechanical cues not only sheds light on cancer progression but also holds promise for identifying potential biomarkers that would predict therapeutic outcomes. However, standardizing methods for studying how mechanical cues affect tumor progression is challenging. This challenge stems from the limitations of traditional in vitro cell culture systems, which fail to encompass the critical contextual cues present in vivo. To address this, 3D tumor spheroids have been established as a preferred model, more closely mimicking cancer progression, but they usually lack reproduction of the mechanical microenvironment encountered in actual solid tumors. Here, we review the role of mechanical forces in modulating tumor- and immune-cell responses and discuss how grasping the importance of these mechanical cues could revolutionize in vitro tumor tissue engineering. The creation of more physiologically relevant environments that better replicate in vivo conditions will eventually increase the efficacy of currently available treatments, including immunotherapies.

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Section: Conclusive Remarks and Remaining Challengesmentioning

confidence: 99%

Toward innovative approaches for exploring the mechanically regulated tumor-immune microenvironment

Kalli,

Stylianopoulos

2024

APL Bioengineering

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“…Cells may be suspended in a medium and flowed into the device to adhere to walls or biomaterials, or they may be introduced into biomaterial solutions and plotted into specific positions. [ 100 ] In other cases, they are first turned into spheroids or aggregates and then further mixed in biomaterial solutions or placed in spatially relevant locations. Sliced tissues from real tumors may additionally be seeded in biomaterials or placed in microfluidic chambers.…”

Section: Biofabrication Of Tumor Microenvironment (Tme)mentioning

confidence: 99%

“…Subsequently, mediums, factors, and genes, which are non‐cellular entities, are added to the scaffold/matrix or flowed through microfluidic paths to nourish and stimulate the cells toward maturation. [ 100 ] Factors and genes may not always be added since they can be directly produced by cells. However, they may be added to simulate a specific period in the tumor cascade.…”

Section: Biofabrication Of Tumor Microenvironment (Tme)mentioning

confidence: 99%

Cancer Models on Chip: Paving the Way to Large‐Scale Trial Applications

et al. 2023

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Cancer kills millions of individuals every year all over the world (Global Cancer Observatory). The physiological and biomechanical processes underlying the tumor are still poorly understood, hindering researchers from creating new, effective therapies. Inconsistent results of preclinical research, in vivo testing, and clinical trials decrease drug approval rates. 3D tumor‐on‐a‐chip (ToC) models integrate biomaterials, tissue engineering, fabrication of microarchitectures, and sensory and actuation systems in a single device, enabling reliable studies in fundamental oncology and pharmacology. This review includes a critical discussion about their ability to reproduce the tumor microenvironment (TME), the advantages and drawbacks of existing tumor models and architectures, major components and fabrication techniques. The focus is on current materials and micro/nanofabrication techniques used to manufacture reliable and reproducible microfluidic ToC models for large‐scale trial applications.

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“…It might also bring discrepancies between in vitro and in vivo testing. Microfluidic technologies have been adopted to develop in vitro physiological models by creating a tissue environment and its structural function [ 15 , 16 , 17 ]. Recently, many gut chips have been developed over two decades and gradually evolved from a simple 2D culture system to a complex 3D intestine tumor model.…”

Section: Introductionmentioning

confidence: 99%

Simulating the Effect of Gut Microbiome on Cancer Cell Growth Using a Microfluidic Device

Mittal

Cupp

Kang

2023

Sensors

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The imbalance in the gut microbiome plays a vital role in the progression of many diseases, including cancer, due to increased inflammation in the body. Since gut microbiome-induced inflammation can serve as a novel therapeutic strategy, there is an increasing need to identify novel approaches to investigate the effect of inflammation instigated by gut microbiome on cancer cells. However, there are limited biomimetic co-culture systems that allow testing of the causal relationship of the microbiome on cancer cells. Here we developed a microfluidic chip that can simulate the interaction of the gut microbiome and cancer cells to investigate the effects of bacteria and inflammatory stress on cancer cells in vitro. To test the microfluidic chip, we used colorectal cancer cells, as an increased microbiome abundance has been associated with poor outcomes in colorectal cancer. We cultured colorectal cancer cells with Bacillus bacteria or lipopolysaccharide (LPS), a purified bacterial membrane that induces a significant inflammatory response, in the microfluidic device. Our results showed that both LPS and Bacillus significantly accelerated the growth of colorectal cancer cells, therefore supporting that the increased presence of certain bacteria promotes cancer cell growth. The microfluidic device included in this study may have significant implications in identifying new treatments for various cancer types in the future.

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The Applications and Challenges of the Development of In Vitro Tumor Microenvironment Chips

Cited by 9 publications

References 123 publications

Toward innovative approaches for exploring the mechanically regulated tumor-immune microenvironment

Toward innovative approaches for exploring the mechanically regulated tumor-immune microenvironment

Cancer Models on Chip: Paving the Way to Large‐Scale Trial Applications

Simulating the Effect of Gut Microbiome on Cancer Cell Growth Using a Microfluidic Device

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