Biomimetic tumor microenvironment on a microfluidic platform

Ma, Huipeng; Xu, Hui; Qin, Jianhua

doi:10.1063/1.4774070

Cited by 43 publications

(29 citation statements)

References 102 publications

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“…Microfluidic devices enable the creation of specific organ microenvironment, generation of particular signaling cues, and experimentation with different cancer cell types. 40 Furthermore, they allow quantitative analysis of various control parameters as well as convenient optical access for continuous monitoring and recording of events within the devices. Recently, several microfluidic systems were employed to study cell migration and tumor cell intravasation.…”

Section: Introductionmentioning

confidence: 99%

A microfluidic model for organ-specific extravasation of circulating tumor cells

et al. 2014

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Circulating tumor cells (CTCs) are the principal vehicle for the spread of non-hematologic cancer disease from a primary tumor, involving extravasation of CTCs across blood vessel walls, to form secondary tumors in remote organs. Herein, a polydimethylsiloxane-based microfluidic system is developed and characterized for in vitro systematic studies of organ-specific extravasation of CTCs. The system recapitulates the two major aspects of the in vivo extravasation microenvironment: local signaling chemokine gradients in a vessel with an endothelial monolayer. The parameters controlling the locally stable chemokine gradients, flow rate, and initial chemokine concentration are investigated experimentally and numerically. The microchannel surface treatment effect on the confluency and adhesion of the endothelial monolayer under applied shear flow has also been characterized experimentally. Further, the conditions for driving a suspension of CTCs through the microfluidic system are discussed while simultaneously maintaining both the local chemokine gradients and the confluent endothelial monolayer. Finally, the microfluidic system is utilized to demonstrate extravasation of MDA-MB-231 cancer cells in the presence of CXCL12 chemokine gradients. Consistent with the hypothesis of organ-specific extravasation, control experiments are presented to substantiate the observation that the MDA-MB-231 cell migration is attributed to chemotaxis rather than a random process.

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Section: Introductionmentioning

confidence: 99%

A microfluidic model for organ-specific extravasation of circulating tumor cells

et al. 2014

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“…An in vitro model recapitulating the cancer cells as well as their microenvironment can enable more biomimetic and clinically relevant outcomes to accelerate our knowledge in tumour biology and improve cancer therapeutic development. In this section, we briefly review the microdevices developed in the past few decades to study different TMEs, including the peri-necrotic niche, peri-vascular niche and metastatic niche [122,124,132].…”

Section: Mimicking Tumour Microenvironment Using Microdevicesmentioning

confidence: 99%

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

Tsai

Trubelja

Shen

et al. 2017

J. R. Soc. Interface.

179

133

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Cancer remains one of the leading causes of death, albeit enormous efforts to cure the disease. To overcome the major challenges in cancer therapy, we need to have a better understanding of the tumour microenvironment (TME), as well as a more effective means to screen anti-cancer drug leads; both can be achieved using advanced technologies, including the emerging tumour-on-a-chip technology. Here, we review the recent development of the tumour-on-a-chip technology, which integrates microfluidics, microfabrication, tissue engineering and biomaterials research, and offers new opportunities for building and applying functional three-dimensional in vitro human tumour models for oncology research, immunotherapy studies and drug screening. In particular, tumour-on-a-chip microdevices allow well-controlled microscopic studies of the interaction among tumour cells, immune cells and cells in the TME, of which simple tissue cultures and animal models are not amenable to do. The challenges in developing the next-generation tumour-on-a-chip technology are also discussed.

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“…Even though great advances have been made in this context, elucidation of precise interactions between different members of the cancer cells' microenvironment remains an object of intense investigation. The development and gradual implementation of appropriate technologies such as nanotechnologybased microfluidics coupled to microscopy have given rise to encouraging studies on the multi-faceted composition of ''cancer microenvironments'' (Ma et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

A multidisciplinary study usingin vivotumor models and microfluidic cell-on-chip approach to explore the cross-talk between cancer and immune cells

Mattei

Schiavoni

Ninno

et al. 2014

Journal of Immunotoxicology

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(2014) A multidisciplinary study using invivo tumor models and microfluidic cell-on-chip approach to explore the crosstalk between cancer and immune cells, Journal of Immunotoxicology, 11:4,[337][338][339][340][341][342][343][344][345][346] AbstractA full elucidation of events occurring inside the cancer microenvironment is fundamental for the optimization of more effective therapies. In the present study, the cross-talk between cancer and immune cells was examined by employing mice deficient (KO) in interferon regulatory factor (IRF)-8, a transcription factor essential for induction of competent immune responses. The in vivo results showed that IRF-8 KO mice were highly permissive to B16.F10 melanoma growth and metastasis due to failure of their immune cells to exert proper immunosurveillance. These events were found to be dependent on soluble factors released by cells of the immune system capable of shaping the malignant phenotype of melanoma cells. An on-chip model was then generated to further explore the reciprocal interactions between the B16.F10 and immune cells. B16.F10 and immune cells were co-cultured in a microfluidic device composed of three culturing chambers suitably inter-connected by an array of microchannels; mutual interactions were then followed using time-lapse microscopy. It was observed that WT immune cells migrated through the microchannels towards the B16.F10 cells, establishing tight interactions that in turn limited tumor spread. In contrast, IRF-8 KO immune cells poorly interacted with the melanoma cells, resulting in a more invasive behavior of the B16.F10 cells. These results suggest that IRF-8 expression plays a key role in the cross-talk between melanoma and immune cells, and under-score the value of cell-on-chip approaches as useful in vitro tools to reconstruct complex in vivo microenvironments on a microscale level to explore cell interactions such as those occurring within a cancer immunoenvironment.

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Biomimetic tumor microenvironment on a microfluidic platform

Cited by 43 publications

References 102 publications

A microfluidic model for organ-specific extravasation of circulating tumor cells

A microfluidic model for organ-specific extravasation of circulating tumor cells

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

A multidisciplinary study usingin vivotumor models and microfluidic cell-on-chip approach to explore the cross-talk between cancer and immune cells

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