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Spheroid Formation of Hepatocarcinoma Cells in Microwells: Experiments and Monte Carlo Simulations

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

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 low-adhesion 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.

Suggested Citation

  • Yan Wang & Myung Hee Kim & Seyed R Tabaei & Jae Hyeok Park & Kyuhwan Na & Seok Chung & Vladimir P Zhdanov & Nam-Joon Cho, 2016. "Spheroid Formation of Hepatocarcinoma Cells in Microwells: Experiments and Monte Carlo Simulations," PLOS ONE, Public Library of Science, vol. 11(8), pages 1-13, August.
  • Handle: RePEc:plo:pone00:0161915
    DOI: 10.1371/journal.pone.0161915
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    References listed on IDEAS

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    1. Zhdanov, Vladimir P., 2008. "Simulation of proliferation and differentiation of cells in a stem-cell niche," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 387(24), pages 6126-6136.
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    1. Zhdanov, Vladimir P., 2009. "Signal propagation in stem-cell niches," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 388(18), pages 3791-3797.

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