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Article

Engineering a Vascularized Hypoxic Tumor Model for Therapeutic Assessment

1
Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA 90089, USA
2
Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
3
USC Stem Cell, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
*
Author to whom correspondence should be addressed.
Academic Editors: María Yáñez-Mó, Hector Peinado, Esther M. Lafuente and Carlos Cabañas
Cells 2021, 10(9), 2201; https://doi.org/10.3390/cells10092201
Received: 15 July 2021 / Revised: 23 August 2021 / Accepted: 23 August 2021 / Published: 26 August 2021
Solid tumors in advanced cancer often feature a structurally and functionally abnormal vasculature through tumor angiogenesis, which contributes to cancer progression, metastasis, and therapeutic resistances. Hypoxia is considered a major driver of angiogenesis in tumor microenvironments. However, there remains a lack of in vitro models that recapitulate both the vasculature and hypoxia in the same model with physiological resemblance to the tumor microenvironment, while allowing for high-content spatiotemporal analyses for mechanistic studies and therapeutic evaluations. We have previously constructed a hypoxia microdevice that utilizes the metabolism of cancer cells to generate an oxygen gradient in the cancer cell layer as seen in solid tumor sections. Here, we have engineered a new composite microdevice-microfluidics platform that recapitulates a vascularized hypoxic tumor. Endothelial cells were seeded in a collagen channel formed by viscous fingering, to generate a rounded vascular lumen surrounding a hypoxic tumor section composed of cancer cells embedded in a 3-D hydrogel extracellular matrix. We demonstrated that the new device can be used with microscopy-based high-content analyses to track the vascular phenotypes, morphology, and sprouting into the hypoxic tumor section over a 7-day culture, as well as the response to different cancer/stromal cells. We further evaluated the integrity/leakiness of the vascular lumen in molecular delivery, and the potential of the platform to study the movement/trafficking of therapeutic immune cells. Therefore, our new platform can be used as a model for understanding tumor angiogenesis and therapeutic delivery/efficacy in vascularized hypoxic tumors. View Full-Text
Keywords: vasculature; angiogenesis; tumor microenvironment; hypoxia; viscous fingering vasculature; angiogenesis; tumor microenvironment; hypoxia; viscous fingering
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MDPI and ACS Style

Ando, Y.; Oh, J.M.; Zhao, W.; Tran, M.; Shen, K. Engineering a Vascularized Hypoxic Tumor Model for Therapeutic Assessment. Cells 2021, 10, 2201. https://doi.org/10.3390/cells10092201

AMA Style

Ando Y, Oh JM, Zhao W, Tran M, Shen K. Engineering a Vascularized Hypoxic Tumor Model for Therapeutic Assessment. Cells. 2021; 10(9):2201. https://doi.org/10.3390/cells10092201

Chicago/Turabian Style

Ando, Yuta, Jeong M. Oh, Winfield Zhao, Madeleine Tran, and Keyue Shen. 2021. "Engineering a Vascularized Hypoxic Tumor Model for Therapeutic Assessment" Cells 10, no. 9: 2201. https://doi.org/10.3390/cells10092201

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