Tumor-on-a-chip: a microfluidic model to study cell response to environmental gradients

Ayuso, Jesús Manso; Virumbrales-Muñoz, María; McMinn, Patrick H.; Rehman, Shujah; Gómez, Iván; Karim, Mohammad Rezaul; Trusttchel, Regan; Wisinski, Kari B.; Beebe, David J.; Skala, Melissa C.

doi:10.1039/c9lc00270g

Cited by 76 publications

(69 citation statements)

References 40 publications

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“…The results observed in the tumor-on-a-chip platform demonstrated a correlation between the generation of a necrotic core and the presence of pH gradients. In addition, in a previous study, we observed that oxygen played a minor role in the generation of the necrotic core, leading to a moderate increase in the number of dead cells observed in the distal region ( 13 ). Our platform is permeable to oxygen, demonstrating that MCF7 cells did not generate hypoxia within the microdevice at 30 million cells/ml ( 19 ).…”

Section: Discussionmentioning

confidence: 64%

“…Therefore, the development of new tools that allow researchers to decipher the complex mechanisms driving immune exhaustion could accelerate the development of next-generation immunotherapies ( 12 ). In this context, our tumor-on-a-chip platform provides a simple and versatile tool to evaluate the effect of environmental stress such as nutrient deprivation, acidic pH, or waste product accumulation ( 13 ). Immune penetration into solid tumors affects tumor evolution and remains an active research area in the immunotherapy community.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, understanding the consequences of the environmental stress on immune cells is critical to develop more effective immunotherapies ( 10 , 11 ). However, capturing the complexity of the solid tumor microenvironment (TME) with traditional two-dimensional (2D) models remains challenging ( 12 , 13 ).…”

Section: Introductionmentioning

confidence: 99%

“…Commonly, microdevices generate gradients by perfusing two parallel streams of liquid (e.g., medium with 20 and 1% O 2 ) to create a gradient across the microdevice leveraging passive diffusion ( 18 ). Thus, here, we have evaluated the influence of the tumor environmental stress on NK cell functions using a tumor-on-a-chip model ( 13 , 19 ). Our tumor-on-a-chip model includes a microchamber where breast cancer cells were embedded in a 3D matrix.…”

Section: Introductionmentioning

confidence: 99%

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Microfluidic tumor-on-a-chip model to evaluate the role of tumor environmental stress on NK cell exhaustion

et al. 2021

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Solid tumors generate a suppressive environment that imposes an overwhelming burden on the immune system. Nutrient depletion, waste product accumulation, hypoxia, and pH acidification severely compromise the capacity of effector immune cells such as T and natural killer (NK) cells to destroy cancer cells. However, the specific molecular mechanisms driving immune suppression, as well as the capacity of immune cells to adapt to the suppressive environment, are not completely understood. Thus, here, we used an in vitro microfluidic tumor-on-a-chip platform to evaluate how NK cells respond to the tumor-induced suppressive environment. The results demonstrated that the suppressive environment created by the tumor gradually eroded NK cell cytotoxic capacity, leading to compromised NK cell surveillance and tumor tolerance. Further, NK cell exhaustion persisted for an extended period of time after removing NK cells from the microfluidic platform. Last, the addition of checkpoint inhibitors and immunomodulatory agents alleviated NK cell exhaustion.

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Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Microfluidic tumor-on-a-chip model to evaluate the role of tumor environmental stress on NK cell exhaustion

et al. 2021

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“…Therefore, the bleaching mechanism might not only be resulted from the reactive oxygen species produced by zooxanthellae to damaged the coral host cells but also associated with DO, DIC, and nutrition uptaking [15,18,44]. However, in order to fully address this issue, a more in-depth investigation should be conducted in the near future, for example microsensors for detecting chemical substances can be integrated [45,46].…”

Section: Discussionmentioning

confidence: 99%

Miniaturized Platform for Individual Coral Polyps Culture and Monitoring

Luo

Zhao

et al. 2020

Micromachines

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Methodologies for coral polyps culture and real-time monitoring are important in investigating the effects of the global environmental changes on coral reefs and marine biology. However, the traditional cultivation method is limited in its ability to provide a rapid and dynamic microenvironment to effectively exchange the chemical substances and simulate the natural environment change. Here, an integrated microdevice with continuous perfusion and temperature-control in the microenvironment was fabricated for dynamic individual coral polyps culture. For a realistic mimicry of the marine ecological environment, we constructed the micro-well based microfluidics platform that created a fluid flow environment with a low shear rate and high substance transfer, and developed a sensitive temperature control system for the long-term culture of individual coral polyps. This miniaturized platform was applied to study the individual coral polyps in response to the temperature change for evaluating the coral death caused by El Nino. The experimental results demonstrated that the microfluidics platform could provide the necessary growth environment for coral polyps as expected so that in turn the biological activity of individual coral polyps can quickly be recovered. The separation between the algae and host polyp cells were observed in the high culture temperature range and the coral polyp metabolism was negatively affected. We believe that our culture platform for individual coral polyps can provide a reliable analytical approach for model and mechanism investigations of coral bleaching and reef conservation.

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Advanced Bioresponsive Multitasking Hydrogels in the New Era of Biomedicine

Niazi

Alizadeh

Zarebkohan

et al. 2021

Adv Funct Materials

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Advanced forms of hydrogels have many inherently desirable properties and can be designed with different structures and functions. In particular, bioresponsive multifunctional hydrogels can carry out sophisticated biological functions. These include in situ single-cell approaches, capturing, analysis, and release of living cells, biomimetics of cell, tissue, and tumor-specific niches. They can allow in vivo cell manipulation and act as novel drug delivery systems, allowing diagnostic, therapeutic, vaccination, and immunotherapy methods. In the present review of multitasking hydrogels, new approaches and devices classified into point-of-care testing (POCT), microarrays, single-cell/rare cell approaches, artificial membranes, biomimetic modeling systems, nanodoctors, and microneedle patches are summarized. The potentials and application of each format are critically discussed, and some limitations are highlighted. Finally, how hydrogels can enable an "all-in-one platform" to play a key role in cancer therapy, regenerative medicine, and the treatment of inflammatory, degenerative, genetic, and metabolic diseases is being looked forward to.

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Tumor-on-a-chip: a microfluidic model to study cell response to environmental gradients

Abstract: Limited blood supply and rapid tumor metabolism within solid tumors leads to nutrient starvation, waste product accumulation and the generation of pH gradients across the tumor mass.

Cited by 76 publications

References 40 publications

Microfluidic tumor-on-a-chip model to evaluate the role of tumor environmental stress on NK cell exhaustion

Microfluidic tumor-on-a-chip model to evaluate the role of tumor environmental stress on NK cell exhaustion

Miniaturized Platform for Individual Coral Polyps Culture and Monitoring

Advanced Bioresponsive Multitasking Hydrogels in the New Era of Biomedicine

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