High-throughput microfluidic 3D biomimetic model enabling quantitative description of the human breast tumor microenvironment

Fridman, Ilana Berger; Kostas, James; Greguš, Michal; Ray, Somak; Sullivan, Matthew R.; Ivanov, Alexander R.; Cohen, Smadar; Konry, Tania

doi:10.1016/j.actbio.2021.06.025

Cited by 26 publications

(13 citation statements)

References 111 publications

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“…Additionally, a majority of TAMs presented as resting cells or low secretors, suggesting a potential to be re-educated towards favoring an effective anti-tumor response [21,53,54] Interestingly, we found that TAM heterogeneity is lost when isolated and cultured ex vivo in 2D conditions, emphasizing the need for TME signals to maintain their identity. In recent years, 3D cultures in hydrogels, including collagen [55,56], have provided valuable tools to accelerate tumor studies and TME modeling [33,34]. In the present study, we developed a 3D collagen co-culture system to mimic the melanoma TME and investigate how interactions between melanoma cells, fibroblasts, and macrophages shape the early stages of macrophage immune activity leading to such complex phenotypes.…”

Section: Discussionmentioning

confidence: 99%

3D Model of the Early Melanoma Microenvironment Captures Macrophage Transition into a Tumor-Promoting Phenotype

Pizzurro

Liu

Bridges

et al. 2021

Cancers

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Tumor immune response is shaped by the tumor microenvironment (TME), which often evolves to be immunosuppressive, promoting disease progression and metastasis. An important example is melanoma tumors, which display high numbers of tumor-associated macrophages (TAMs) that are immunosuppressive but also have the potential to restore anti-tumor activity. However, to therapeutically target TAMs, there is a need to understand the early events that shape their tumor-promoting profile. To address this, we built and optimized 3D in vitro co-culture systems, composed of a collagen-I matrix scaffolding murine bone-marrow-derived macrophages (BMDMs), YUMM1.7 melanoma cells, and fibroblasts to recreate the early melanoma TME and study how interactions with fibroblasts and tumor cells modulate macrophage immune activity. We monitored BMDM behavior and interactions through time-lapse imaging and characterized their activation and secretion. We found that stromal cells induced a rapid functional activation, with increased motility and response from BMDMs. Over the course of seven days, BMDMs acquired a phenotype and secretion profile that resembled melanoma TAMs in established tumors. Overall, the direct cell–cell interactions with the stromal components in a 3D environment shape BMDM transition to a TAM-like immunosuppressive state. Our systems will enable future studies of changes in macrophage–stromal cross-talk in the melanoma TME

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Section: Discussionmentioning

confidence: 99%

3D Model of the Early Melanoma Microenvironment Captures Macrophage Transition into a Tumor-Promoting Phenotype

Pizzurro

Liu

Bridges

et al. 2021

Cancers

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“…Collagen and other scaffolding proteins have been connected to the illness's invasiveness and metastatic potential [103]. Hypoxia and necrosis are more likely to occur in tumors with reduced blood vessel constriction, which decreases oxygen transmission [264,265]. Because restriction decreases blood flow, it also decreases the effectiveness of therapeutic therapies.…”

Section: Microfluidic Design Considerationsmentioning

confidence: 99%

Functional biomaterials for biomimetic 3D in vitro tumor microenvironment modeling

Ahmed

2023

In vitro models

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The translational potential of promising anticancer medications and treatments may be enhanced by the creation of 3D in vitro models that can accurately reproduce native tumor microenvironments. Tumor microenvironments for cancer treatment and research can be built in vitro using biomaterials. Three-dimensional in vitro cancer models have provided new insights into the biology of cancer. Cancer researchers are creating artificial three-dimensional tumor models based on functional biomaterials that mimic the microenvironment of the real tumor. Our understanding of tumor stroma activity over the course of cancer has improved because of the use of scaffold and matrix-based three-dimensional systems intended for regenerative medicine. Scientists have created synthetic tumor models thanks to recent developments in materials engineering. These models enable researchers to investigate the biology of cancer and assess the therapeutic effectiveness of available medications. The emergence of biomaterial engineering technologies with the potential to hasten treatment outcomes is highlighted in this review, which also discusses the influence of creating in vitro biomimetic 3D tumor microenvironments utilizing functional biomaterials. Future cancer treatments will rely much more heavily on biomaterials engineering.

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“…In another study, Strelez et al [ 289 ] presented the colorectal cancer (CRC) on-a-chip platforms with the facets of CRC, stromal cross-talk, and mechanical force. Moreover, Fridman et al [ 305 ] mimicked the breast tumor microenvironment, where tumor cells, immune cells, and fibroblasts were encapsulated into different hydrogel scaffolds within a microfluidic platform. Similarly, Haque et al [ 290 ] used patient-derived organoids and mimicked pancreatic ductal adenocarcinoma by exhibiting epithelium–stroma communication and controlled the microenvironment-modulating agents in a lab-on-a-chip model.…”

Section: Biomedical Applicationsmentioning

confidence: 99%

Biomedical Applications of Microfluidic Devices: A Review

et al. 2022

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Both passive and active microfluidic chips are used in many biomedical and chemical applications to support fluid mixing, particle manipulations, and signal detection. Passive microfluidic devices are geometry-dependent, and their uses are rather limited. Active microfluidic devices include sensors or detectors that transduce chemical, biological, and physical changes into electrical or optical signals. Also, they are transduction devices that detect biological and chemical changes in biomedical applications, and they are highly versatile microfluidic tools for disease diagnosis and organ modeling. This review provides a comprehensive overview of the significant advances that have been made in the development of microfluidics devices. We will discuss the function of microfluidic devices as micromixers or as sorters of cells and substances (e.g., microfiltration, flow or displacement, and trapping). Microfluidic devices are fabricated using a range of techniques, including molding, etching, three-dimensional printing, and nanofabrication. Their broad utility lies in the detection of diagnostic biomarkers and organ-on-chip approaches that permit disease modeling in cancer, as well as uses in neurological, cardiovascular, hepatic, and pulmonary diseases. Biosensor applications allow for point-of-care testing, using assays based on enzymes, nanozymes, antibodies, or nucleic acids (DNA or RNA). An anticipated development in the field includes the optimization of techniques for the fabrication of microfluidic devices using biocompatible materials. These developments will increase biomedical versatility, reduce diagnostic costs, and accelerate diagnosis time of microfluidics technology.

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High-throughput microfluidic 3D biomimetic model enabling quantitative description of the human breast tumor microenvironment

Cited by 26 publications

References 111 publications

3D Model of the Early Melanoma Microenvironment Captures Macrophage Transition into a Tumor-Promoting Phenotype

3D Model of the Early Melanoma Microenvironment Captures Macrophage Transition into a Tumor-Promoting Phenotype

Functional biomaterials for biomimetic 3D in vitro tumor microenvironment modeling

Biomedical Applications of Microfluidic Devices: A Review

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