Facile Tumor Spheroids Formation in Large Quantity with Controllable Size and High Uniformity

Abstract A facile method for generation of tumor spheroids in large quantity with controllable size and high uniformity is presented. HCT-116 cells are used as a model cell line. Individual tumor cells are sparsely seeded onto petri-dishes. After a few days of growth, separated cellular islets are f...

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Main Authors: Wentao Shi, Jean Kwon, Yongyang Huang, Jifu Tan, Christopher G. Uhl, Ran He, Chao Zhou, Yaling Liu
Format: Article
Language:English
Published: Nature Portfolio 2018-05-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-018-25203-3
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author Wentao Shi
Jean Kwon
Yongyang Huang
Jifu Tan
Christopher G. Uhl
Ran He
Chao Zhou
Yaling Liu
author_facet Wentao Shi
Jean Kwon
Yongyang Huang
Jifu Tan
Christopher G. Uhl
Ran He
Chao Zhou
Yaling Liu
author_sort Wentao Shi
collection DOAJ
description Abstract A facile method for generation of tumor spheroids in large quantity with controllable size and high uniformity is presented. HCT-116 cells are used as a model cell line. Individual tumor cells are sparsely seeded onto petri-dishes. After a few days of growth, separated cellular islets are formed and then detached by dispase while maintaining their sheet shape. These detached cell sheets are transferred to dispase-doped media under orbital shaking conditions. Assisted by the shear flow under shaking and inhibition of cell-to-extracellular matrix junctions by dispase, the cell sheets curl up and eventually tumor spheroids are formed. The average size of the spheroids can be controlled by tuning the cell sheet culturing period and spheroid shaking period. The uniformity can be controlled by a set of sieves which were home-made using stainless steel meshes. Since this method is based on simple petri-dish cell culturing and shaking, it is rather facile for forming tumor spheroids with no theoretical quantity limit. This method has been used to form HeLa, A431 and U87 MG tumor spheroids and application of the formed tumor spheroids in drug screening is also demonstrated. The viability, 3D structure, and necrosis of the spheroids are characterized.
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spelling doaj.art-6e9f196f95c54b0eaee8ea5759b016252022-12-21T20:35:12ZengNature PortfolioScientific Reports2045-23222018-05-01811910.1038/s41598-018-25203-3Facile Tumor Spheroids Formation in Large Quantity with Controllable Size and High UniformityWentao Shi0Jean Kwon1Yongyang Huang2Jifu Tan3Christopher G. Uhl4Ran He5Chao Zhou6Yaling Liu7Department of Bioengineering, Lehigh UniversityDepartment of Bioengineering, Lehigh UniversityDepartment of Electrical and Computer Engineering, Lehigh UniversityDepartment of Mechanical Engineering, Northern Illinois UniversityDepartment of Bioengineering, Lehigh UniversityDepartment of Mechanical Engineering and Mechanics, Lehigh UniversityDepartment of Bioengineering, Lehigh UniversityDepartment of Bioengineering, Lehigh UniversityAbstract A facile method for generation of tumor spheroids in large quantity with controllable size and high uniformity is presented. HCT-116 cells are used as a model cell line. Individual tumor cells are sparsely seeded onto petri-dishes. After a few days of growth, separated cellular islets are formed and then detached by dispase while maintaining their sheet shape. These detached cell sheets are transferred to dispase-doped media under orbital shaking conditions. Assisted by the shear flow under shaking and inhibition of cell-to-extracellular matrix junctions by dispase, the cell sheets curl up and eventually tumor spheroids are formed. The average size of the spheroids can be controlled by tuning the cell sheet culturing period and spheroid shaking period. The uniformity can be controlled by a set of sieves which were home-made using stainless steel meshes. Since this method is based on simple petri-dish cell culturing and shaking, it is rather facile for forming tumor spheroids with no theoretical quantity limit. This method has been used to form HeLa, A431 and U87 MG tumor spheroids and application of the formed tumor spheroids in drug screening is also demonstrated. The viability, 3D structure, and necrosis of the spheroids are characterized.https://doi.org/10.1038/s41598-018-25203-3
spellingShingle Wentao Shi
Jean Kwon
Yongyang Huang
Jifu Tan
Christopher G. Uhl
Ran He
Chao Zhou
Yaling Liu
Facile Tumor Spheroids Formation in Large Quantity with Controllable Size and High Uniformity
Scientific Reports
title Facile Tumor Spheroids Formation in Large Quantity with Controllable Size and High Uniformity
title_full Facile Tumor Spheroids Formation in Large Quantity with Controllable Size and High Uniformity
title_fullStr Facile Tumor Spheroids Formation in Large Quantity with Controllable Size and High Uniformity
title_full_unstemmed Facile Tumor Spheroids Formation in Large Quantity with Controllable Size and High Uniformity
title_short Facile Tumor Spheroids Formation in Large Quantity with Controllable Size and High Uniformity
title_sort facile tumor spheroids formation in large quantity with controllable size and high uniformity
url https://doi.org/10.1038/s41598-018-25203-3
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