Spheroid formation of hepatocarcinoma cells in microwells: Experiments and Monte Carlo simulations

Yan Wang; Myung Hee Kim; Seyed R. Tabaei; Jae Hyeok Park; Kyuhwan Na; Seok Chung; Vladimir P. Zhdanov; Nam Joon Cho

doi:10.1371/journal.pone.0161915

Spheroid formation of hepatocarcinoma cells in microwells: Experiments and Monte Carlo simulations

Yan Wang, Myung Hee Kim, Seyed R. Tabaei, Jae Hyeok Park, Kyuhwan Na, Seok Chung, Vladimir P. Zhdanov, Nam Joon Cho

Research output: Contribution to journal › Article › peer-review

27 Citations (Scopus)

Abstract

The formation of spherical aggregates during the growth of cell population has long been observed under various conditions. We observed the formation of such aggregates during proliferation of Huh-7.5 cells, a human hepatocarcinoma cell line, in a microfabricated lowadhesion microwell system (SpheroFilm; formed of mass-producible silicone elastomer) on the length scales up to 500 μm. The cell proliferation was also tracked with immunofluorescence staining of F-actin and cell proliferation marker Ki-67. Meanwhile, our complementary 3D Monte Carlo simulations, taking cell diffusion and division, cell-cell and cell-scaffold adhesion, and gravity into account, illustrate the role of these factors in the formation of spheroids. Taken together, our experimental and simulation results provide an integrative view of the process of spheroid formation for Huh-7.5 cells.

Original language	English
Article number	e0161915
Journal	PLoS One
Volume	11
Issue number	8
DOIs	https://doi.org/10.1371/journal.pone.0161915
Publication status	Published - Aug 2016
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2016 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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title = "Spheroid formation of hepatocarcinoma cells in microwells: Experiments and Monte Carlo simulations",

abstract = "The formation of spherical aggregates during the growth of cell population has long been observed under various conditions. We observed the formation of such aggregates during proliferation of Huh-7.5 cells, a human hepatocarcinoma cell line, in a microfabricated lowadhesion microwell system (SpheroFilm; formed of mass-producible silicone elastomer) on the length scales up to 500 μm. The cell proliferation was also tracked with immunofluorescence staining of F-actin and cell proliferation marker Ki-67. Meanwhile, our complementary 3D Monte Carlo simulations, taking cell diffusion and division, cell-cell and cell-scaffold adhesion, and gravity into account, illustrate the role of these factors in the formation of spheroids. Taken together, our experimental and simulation results provide an integrative view of the process of spheroid formation for Huh-7.5 cells.",

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note = "Publisher Copyright: {\textcopyright} 2016 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",

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AU - Wang, Yan

AU - Kim, Myung Hee

AU - Tabaei, Seyed R.

AU - Park, Jae Hyeok

AU - Na, Kyuhwan

AU - Chung, Seok

AU - Zhdanov, Vladimir P.

AU - Cho, Nam Joon

N1 - Publisher Copyright: © 2016 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2016/8

Y1 - 2016/8

N2 - The formation of spherical aggregates during the growth of cell population has long been observed under various conditions. We observed the formation of such aggregates during proliferation of Huh-7.5 cells, a human hepatocarcinoma cell line, in a microfabricated lowadhesion microwell system (SpheroFilm; formed of mass-producible silicone elastomer) on the length scales up to 500 μm. The cell proliferation was also tracked with immunofluorescence staining of F-actin and cell proliferation marker Ki-67. Meanwhile, our complementary 3D Monte Carlo simulations, taking cell diffusion and division, cell-cell and cell-scaffold adhesion, and gravity into account, illustrate the role of these factors in the formation of spheroids. Taken together, our experimental and simulation results provide an integrative view of the process of spheroid formation for Huh-7.5 cells.

AB - The formation of spherical aggregates during the growth of cell population has long been observed under various conditions. We observed the formation of such aggregates during proliferation of Huh-7.5 cells, a human hepatocarcinoma cell line, in a microfabricated lowadhesion microwell system (SpheroFilm; formed of mass-producible silicone elastomer) on the length scales up to 500 μm. The cell proliferation was also tracked with immunofluorescence staining of F-actin and cell proliferation marker Ki-67. Meanwhile, our complementary 3D Monte Carlo simulations, taking cell diffusion and division, cell-cell and cell-scaffold adhesion, and gravity into account, illustrate the role of these factors in the formation of spheroids. Taken together, our experimental and simulation results provide an integrative view of the process of spheroid formation for Huh-7.5 cells.

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Spheroid formation of hepatocarcinoma cells in microwells: Experiments and Monte Carlo simulations

Abstract

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