A method for the effective formation of hepatocyte spheroids using a biodegradable polymer nanosphere

Gwak, So Jung; Choi, Dongho; Paik, Seung Sam; Cho, Seung Woo; Kim, Sang Soo; Choi, Cha Yong; Kim, Byung Soo

doi:10.1002/jbm.a.30687

Cited by 11 publications

(6 citation statements)

References 51 publications

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“…However, the most previously used cell based assays for cancer drug studies are based two-dimensional (2D) culture which does not take properly into account the three dimensional (3D) characteristics of tumour formation in vivo [4,5]. Suspension culture is frequently used for multicellular spheroid formation but it is not easy to control the size consistency of the spheroids and to handle them for systematic studies [6,7].…”

Section: Accepted Manuscript Introductionmentioning

confidence: 99%

Agarose multi-wells for tumour spheroid formation and anti-cancer drug test

Tang

Liu

Chen

2016

Microelectronic Engineering

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International audienceCell-based assays can be applied to evaluate the efficiency of anti-cancer drugs but the conventional approaches are mostly based on two-dimensional cell culture which is not able to recapitulate the tumour specificity. Here we developed a method to culture millimetre size tumour spheroids that is useful for anticancer drug studies. Agarose multi wells were obtained by casting on polymethylsiloxane (PDMS) mould, which were then used for culture of U87-MG human glioblastoma. As expected, large size tumour spheroids could be generated after 24 h incubation. Comparing to the multi-well systems made of PDMS or polyethylene glycol diacrylate (PEGDA), agarose multi wells are clearly advantageous due to the hydrophobic surface and the high permeability of agarose. After culture for 10 days, the tumour spheroids in agarose wells stopped to grow and the further increase of the cell seeding density had no effect on the final size of the spheroids. To study the anticancer drug effect, combretastatin A-4 (CA4) was added on day 2 or day 4, showing clear effects on the tumour spheroids and cell viability. More importantly, the live/dead cell staining images suggested that an earlier drug treatment was more efficient to prohibit the tumour spheroid growth

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Section: Accepted Manuscript Introductionmentioning

confidence: 99%

Agarose multi-wells for tumour spheroid formation and anti-cancer drug test

Tang

Liu

Chen

2016

Microelectronic Engineering

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“…4,5 One such method is the inclusion of additives to 3-D cultures for improved spheroid formation. Both biological and synthetic additives have been successfully employed, with mechanisms varying between cross-linking agents, 13,14 adhesion stimulation, 15 or rheological modifiers and crowding agents. 16 Supplementation of cross-linking agents has generally been done with extracellular matrix proteins, such as collagen, fibronectin and reconstituted basement membrane matrigel.…”

Section: Introductionmentioning

confidence: 99%

Media additives to promote spheroid circularity and compactness in hanging drop platform

et al. 2015

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Three-dimensional spheroid cultures have become increasingly popular as drug screening platforms, especially with the advent of different high throughput spheroid forming technologies. However, comparing drug efficacy across different cell types in spheroid culture can be difficult due to variations in spheroid morphologies and transport characteristics. Improving the reproducibility of compact, circular spheroids contributes to standardizing and increasing the fidelity of the desired gradient profiles in these drug screening three-dimensional tissue cultures. In this study we discuss the role that circularity and compaction has on spheroids, and demonstrate the impact methylcellulose (MethoCel) and collagen additives in the culture media can contribute to more compact and circular spheroid morphology. We demonstrate that improved spheroid formation is not a simple function of increased viscosity of the different macromolecule additives, suggesting that other macromolecular characteristics contribute to improved spheroid formation. Of the various macromolecular additives tested for hanging drop culture, MethoCel provided the most desirable spheroid formation. Additionally, the higher viscosity of MethoCel-containing media improved the ease of imaging of cellular spheroids within hanging drop cultures by reducing motion-induced image blur.

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“…Gwak et al (44) developed a new method for the effective spheroid formation of hepatocytes by addition of poly (lactic-co-glycolic acid) nanospheres to hepatocyte cultures in spinner flasks although the mechanism is not clear.…”

Section: Polymeric Nanospherementioning

confidence: 99%

Roles of Spheroid Formation of Hepatocytes in Liver Tissue Engineering

Jiang¹,

Kim²,

Cho³

et al. 2010

Int J Stem Cells

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The liver plays an important role in a broad spectrum of physiological functions and detoxifies endogenous and exogenous substances. The liver failure is associated with a high risk of mortality because it is one of important organs in our body. Various bioartificial liver (BAL) systems have been used for clinical trials as a bridge for liver transplantations in patients with liver failure. Long term and stable liver-specific functions of hepatocytes in the development of BAL support systems should be considered. Spheroid formation of hepatocytes enhances liver-specific functions. In this review, hepatocyte spheroid formation methods such as galactose density, topology of extracellular matrix, micromolding technique, hanging-drop culture, non-adhesive surface, positive charged surface, spinner culture, rocked technique, medium component, external forces, coculture system and polymeric nanospheres are explained for enhancing liver-specific functions.

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A method for the effective formation of hepatocyte spheroids using a biodegradable polymer nanosphere

Cited by 11 publications

References 51 publications

Agarose multi-wells for tumour spheroid formation and anti-cancer drug test

Agarose multi-wells for tumour spheroid formation and anti-cancer drug test

Media additives to promote spheroid circularity and compactness in hanging drop platform

Roles of Spheroid Formation of Hepatocytes in Liver Tissue Engineering

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