Tumor spheroid-on-a-chip: a standardized microfluidic culture platform for investigating tumor angiogenesis. 2019

Jihoon Ko, and Jungho Ahn, and Suryong Kim, and Younggyun Lee, and Jungseub Lee, and Dohyun Park, and Noo Li Jeon
Department of Mechanical and Aerospace Engineering, Seoul National University, Seoul 08826, Republic of Korea. njeon@snu.ac.kr.

The field of microfluidics-based three-dimensional (3D) cell culture system is rapidly progressing from academic proof-of-concept studies to valid solutions to real-world problems. Polydimethylsiloxane (PDMS)-based platform has been widely adopted as in vitro platforms for mimicking tumor microenvironment. However, PDMS has not been welcomed as a standardized commercial application for preclinical screening due to inherent material limitations that make it difficult to scale-up production. Here, we present an injection-molded plastic array 3D spheroid culture platform (Sphero-IMPACT). The platform is made of polystyrene (PS) in a standardized 96-well plate format with a user-friendly interface. This interface describes a simpler design that incorporates a tapered hole in the center of the rail to pattern a large spheroid with 3D extracellular matrix and various cell types. This hole is designed to accommodate standard pipette tip for automated system. The platform that mediate open microfluidics allows implement spontaneous fluid patterning with high repeatability from the end user. To demonstrate versatile use of the platform, we developed 3D perfusable blood vessel network and tumor spheroid assays. In addition, we established a tumor spheroid induced angiogenesis model that can be applicable for drug screening. Sphero-IMPACT has the potential to provide a robust and reproducible in vitro assay related to vascularized cancer research. This easy-to-use, ready-to-use platform can be translated into an enhanced preclinical model that faithfully reflects the complex tumor microenvironment.

UI MeSH Term Description Entries
D009389 Neovascularization, Pathologic A pathologic process consisting of the proliferation of blood vessels in abnormal tissues or in abnormal positions. Angiogenesis, Pathologic,Angiogenesis, Pathological,Neovascularization, Pathological,Pathologic Angiogenesis,Pathologic Neovascularization,Pathological Angiogenesis,Pathological Neovascularization
D012015 Reference Standards A basis of value established for the measure of quantity, weight, extent or quality, e.g. weight standards, standard solutions, methods, techniques, and procedures used in diagnosis and therapy. Standard Preparations,Standards, Reference,Preparations, Standard,Standardization,Standards,Preparation, Standard,Reference Standard,Standard Preparation,Standard, Reference
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D005909 Glioblastoma A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures. Astrocytoma, Grade IV,Giant Cell Glioblastoma,Glioblastoma Multiforme,Astrocytomas, Grade IV,Giant Cell Glioblastomas,Glioblastoma, Giant Cell,Glioblastomas,Glioblastomas, Giant Cell,Grade IV Astrocytoma,Grade IV Astrocytomas
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D046210 Microfluidic Analytical Techniques Methods utilizing the principles of MICROFLUIDICS for sample handling, reagent mixing, and separation and detection of specific components in fluids. Microfluidic Analysis,Analyses, Microfluidic,Analysis, Microfluidic,Analytical Technique, Microfluidic,Analytical Techniques, Microfluidic,Microfluidic Analyses,Microfluidic Analytical Technique,Technique, Microfluidic Analytical,Techniques, Microfluidic Analytical
D061307 Human Umbilical Vein Endothelial Cells Endothelial cells that line venous vessels of the UMBILICAL CORD. Human Umbilical Vein Endothelial Cell,Endothelial Cells, Human Umbilical Vein,HUVEC Cells,Cell, HUVEC,Cells, HUVEC,HUVEC Cell
D018874 Spheroids, Cellular Spherical, heterogeneous aggregates of proliferating, quiescent, and necrotic cells in culture that retain three-dimensional architecture and tissue-specific functions. The ability to form spheroids is a characteristic trait of CULTURED TUMOR CELLS derived from solid TUMORS. Cells from normal tissues can also form spheroids. They represent an in-vitro model for studies of the biology of both normal and malignant cells. (From Bjerkvig, Spheroid Culture in Cancer Research, 1992, p4) Multicellular Spheroids,Cellular Spheroid,Cellular Spheroids,Multicellular Spheroid,Spheroid, Cellular,Spheroid, Multicellular,Spheroids, Multicellular
D018929 Cell Culture Techniques Methods for maintaining or growing CELLS in vitro. Cell Culture,Cell Culture Technique,Cell Cultures,Culture Technique, Cell,Culture Techniques, Cell

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