Microphysiological model of renal cell carcinoma to inform anti-angiogenic therapy

Virumbrales-Muñoz, María; Ayuso, Jesús Manso; Loken, Jack R; Denecke, Kathryn M.; Rehman, Shujah; Skala, Melissa C.; Abel, E. Jason; Beebe, David J.

doi:10.1016/j.biomaterials.2022.121454

Cited by 12 publications

(13 citation statements)

References 65 publications

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“…Specifically, the authors recapitulated RCC hallmarks like hypoxia, glycolic metabolism, and sprouting angiogenesis, and then tested the model response to a common anti-angiogenic drug. The authors also demonstrated the same model using patient-derived RCC cells instead of cell lines with equivalent results ( 84 ).…”

Section: Microfluidic (Microphysiological) Modelsmentioning

confidence: 90%

Models of Renal Cell Carcinoma Used to Investigate Molecular Mechanisms and Develop New Therapeutics

et al. 2022

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Modeling renal cell carcinoma is critical to investigating tumor biology and therapeutic mechanisms. Multiple systems have been developed to represent critical components of the tumor and its surrounding microenvironment. Prominent in vitro models include traditional cell cultures, 3D organoid models, and microphysiological devices. In vivo models consist of murine patient derived xenografts or genetically engineered mice. Each system has unique advantages as well as limitations and researchers must thoroughly understand each model to properly investigate research questions. This review addresses common model systems for renal cell carcinoma and critically evaluates their performance and ability to measure tumor characteristics.

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Section: Microfluidic (Microphysiological) Modelsmentioning

confidence: 90%

Models of Renal Cell Carcinoma Used to Investigate Molecular Mechanisms and Develop New Therapeutics

et al. 2022

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“…A hexagonal microfluidic chamber was designed to increase the contact area between the hydrogel and chamber to prevent collapse and fabricated using standard soft lithography techniques. , Polydimethylsiloxane (PDMS) (SYLGARD184, Dow Corning) rods were cast from hypodermic needles (Fisher Scientific, Pittsburgh, PA) . The fibrinogen pregel solution was mixed with 5U/mL of bovine thrombin (CAS-9002-044, Sigma) and injected into the chamber through the side loading ports.…”

Section: Methodsmentioning

confidence: 99%

“…24,25 Polydimethylsiloxane (PDMS) (SYL-GARD184, Dow Corning) rods were cast from hypodermic needles (Fisher Scientific, Pittsburgh, PA). 26 The fibrinogen pregel solution was mixed with 5U/mL of bovine thrombin (CAS-9002-044, Sigma) and injected into the chamber through the side loading ports. After 1 h of polymerization in the incubator, the PDMS rod was extracted, and the HUVEC suspension (8 million/mL) was seeded into the formed tubular channel.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

Adaptable Microfluidic Vessel-on-a-Chip Platform for Investigating Tumor Metastatic Transport in Bloodstream

Zhou

Paul

et al. 2022

Anal. Chem.

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Cancer metastasis counts for 90% of cancer fatalities, and its development process is still a mystery. The dynamic process of tumor metastatic transport in the blood vessel is not well understood, in which some biomechanical factors, such as shear stress and various flow patterns, may have significant impacts. Here, we report a microfluidic vessel-on-achip platform for recapitulating several key metastatic steps of tumor cells in blood vessels on the same chip, including intravasation, circulating tumor cell (CTC) vascular adhesion, and extravasation. Due to its excellent adaptability, our system can reproduce various microenvironments to investigate the specific interactions between CTCs and blood vessels. On the basis of this platform, effects of important biomechanical factors on CTC adhesion such as vascular surface properties and vessel geometry-dependent hemodynamics were specifically inspected. We demonstrated that CTC adhesion is more likely to occur under certain mechano-physiological situations, such as vessels with vascular glycocalyx (VGCX) shedding and hemodynamic disturbances. Finally, computational models of both the fluidic dynamics in vessels and CTC adhesion were established based on the confocal scanned 3D images. The modeling results are believed to provide insights into exploring tumor metastasis progression and inspire new ideas for anticancer therapy development.

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“…In this setup, we observed the generation of hypoxia, secretion of growth factors, and an increase in the angiogenic response of the nearby blood vessel model. 140 Overall, the effects of different levels of hypoxia in the different neovasculogenic mechanisms remain largely understudied and may be therapeutically targetable, therefore creating opportunities for future studies in this topic.…”

Section: Biochemical Factors In Vascular Biologymentioning

confidence: 99%

Microfluidics in vascular biology research: a critical review for engineers, biologists, and clinicians

et al. 2022

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Microphysiological model of renal cell carcinoma to inform anti-angiogenic therapy

Cited by 12 publications

References 65 publications

Models of Renal Cell Carcinoma Used to Investigate Molecular Mechanisms and Develop New Therapeutics

Models of Renal Cell Carcinoma Used to Investigate Molecular Mechanisms and Develop New Therapeutics

Adaptable Microfluidic Vessel-on-a-Chip Platform for Investigating Tumor Metastatic Transport in Bloodstream

Microfluidics in vascular biology research: a critical review for engineers, biologists, and clinicians

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