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Engineering a Vascularized Hypoxic Tumor Model for Therapeutic Assessment.
- Source :
-
Cells [Cells] 2021 Aug 26; Vol. 10 (9). Date of Electronic Publication: 2021 Aug 26. - Publication Year :
- 2021
-
Abstract
- 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.
- Subjects :
- Blood Vessels physiology
Cell Line, Tumor
Endothelial Cells metabolism
Extracellular Matrix metabolism
Humans
Hypoxia pathology
Microfluidics methods
Models, Biological
Neovascularization, Pathologic metabolism
Neovascularization, Pathologic pathology
Oxygen metabolism
Stromal Cells metabolism
Microfluidics instrumentation
Neoplasms blood supply
Tumor Microenvironment physiology
Subjects
Details
- Language :
- English
- ISSN :
- 2073-4409
- Volume :
- 10
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Cells
- Publication Type :
- Academic Journal
- Accession number :
- 34571851
- Full Text :
- https://doi.org/10.3390/cells10092201