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

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

doi:10.1371/journal.pone.0161915

Cited by 24 publications

(13 citation statements)

References 38 publications

(44 reference statements)

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“…We also showed that spheroids from the microwells have larger populations of cells with stem cell-like properties compared with spheroids formed by conventional tumor spheroid culture methods. The microwell-based spheroid culture method provides the following advantages over the hanging drop method and the other developed spheroid culture platforms: an extended culture period of 1030 days due to easy medium changes; ready for co-culture without direct cell-to-cell contact [30]; easy generation of size-controlled cell spheroids; easy growth medium changes in the device due to the shear-free and stress-free structure [31]; ready application to various cell types; and unlimited throughput, given that 361 cell spheroids can be obtained from a single device. Moreover, the microwell mimics the in vivo environment and contains CSC-secreted factors [32].…”

Section: Resultsmentioning

confidence: 99%

Isolation of spheroid-forming single cells from gastric cancer cell lines: enrichment of cancer stem-like cells

et al. 2018

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Isolation of spheroid-forming cells is important to investigate cancer stem cell (CSC) characteristics. However, conventional tumor spheroid culture methods have not proven suitable because the aggregated spheroids generally maintain their original heterogeneity and harbor multiple cells with various characteristics. Here we cultured spheroids using a polydimethylsiloxane microwell-based method and a limiting dilution protocol. We then isolated and enriched for CSCs that formed single cell-derived spheroids from gastric cancer cell lines. Cells from the microwell demonstrated higher self-renewal, increased expression of stem cell markers and resistance to apoptosis compared with spheroid cells made by the traditional method. This novel approach allows efficient cancer stem cell isolation and represents a step forward in cancer stem cell studies.

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Section: Resultsmentioning

confidence: 99%

Isolation of spheroid-forming single cells from gastric cancer cell lines: enrichment of cancer stem-like cells

et al. 2018

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“…Additionally, choosing PS as the microwell substrate is favorable from a biologist’s perspective because PS is the most commonly utilized plastic for in vitro cell culture research. Compared to PDMS [ 28 ] or polyester [ 13 ] microwells, PS is hassle-free for the researchers in terms of the material accessibility, and more amenable in terms of compatibility with different forms of conventional culture plasticwares, such as Petri dishes [ 3 ] or microtiter plates [ 16 ]. In addition, the PS microwell displayed a gentle concave bottom, and curved microwell structures have been reported to promote the aggregation of spheroids [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

A Facile Approach for Rapid Prototyping of Microneedle Molds, Microwells and Micro-Through-Holes in Various Substrate Materials Using CO2 Laser Drilling

Chen

et al. 2020

Biomedicines

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CO2 laser manufacturing has served as an enabling and reliable tool for rapid and cost-effective microfabrication over the past few decades. While a wide range of industrial and biological applications have been studied, the choice of materials fabricated across various laser parameters and systems is often confounded by their complex combinations. We herein presented a unified procedure performed using percussion CO2 laser drilling with a range of laser parameters, substrate materials and various generated microstructures, enabling a variety of downstream tissue/cellular-based applications. Emphasis is placed on delineating the laser drilling effect on different biocompatible materials and proof-of-concept utilities. First, a polydimethylsiloxane (PDMS) microneedle (MN) array mold is fabricated to generate dissolvable polyvinylpyrrolidone/polyvinyl alcohol (PVP/PVA) MNs for transdermal drug delivery. Second, polystyrene (PS) microwells are optimized in a compact array for the formation of size-controlled multicellular tumor spheroids (MCTSs). Third, coverglass is perforated to form a microaperture that can be used to trap/position cells/spheroids. Fourth, the creation of through-holes in PS is validated as an accessible method to create channels that facilitate medium exchange in hanging drop arrays and as a conducive tool for the growth and drug screenings of MCTSs.

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“…In contrast to the hanging drop method, this microwell system enables the changing of the media during incubation. For cell-cell communication, interspheroid interaction is available via paracrine signaling through the media 109 . A rotating wall vessel can be used to induce polarity or to apply fluidic shear stress to the cell spheroid 110 - 112 .…”

Section: Biomimetic Platforms That Replicate the Physiology Of The Tmmentioning

confidence: 99%

Chemoresistance of Cancer Cells: Requirements of Tumor Microenvironment-mimicking In Vitro Models in Anti-Cancer Drug Development

Jo¹,

Choi²,

Kim³

et al. 2018

Theranostics

146

125

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For decades, scientists have been using two-dimensional cell culture platforms for high-throughput drug screening of anticancer drugs. Growing evidence indicates that the results of anti-cancer drug screening vary with the cell culture microenvironment, and this variation has been proposed as a reason for the high failure rate of clinical trials. Since the culture condition-dependent drug sensitivity of anti-cancer drugs may negatively impact the identification of clinically effective drug candidates, more reliable in vitro cancer platforms are urgently needed. In this review article, we provide an overview of how cell culture conditions can alter drug efficacy and highlight the importance of developing more reliable cancer drug testing platforms for use in the drug discovery process. The environmental factors that can alter drug delivery and efficacy are reviewed. Based on these observations of chemoresistant tumor physiology, we summarize the recent advances in the fabrication of in vitro cancer models and the model-dependent cytotoxicity of anti-cancer drugs, with a particular focus on engineered environmental factors in these platforms. It is believed that more physiologically relevant cancer models can revolutionize the drug discovery process.

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

Cited by 24 publications

References 38 publications

Isolation of spheroid-forming single cells from gastric cancer cell lines: enrichment of cancer stem-like cells

Isolation of spheroid-forming single cells from gastric cancer cell lines: enrichment of cancer stem-like cells

A Facile Approach for Rapid Prototyping of Microneedle Molds, Microwells and Micro-Through-Holes in Various Substrate Materials Using CO2 Laser Drilling

Chemoresistance of Cancer Cells: Requirements of Tumor Microenvironment-mimicking In Vitro Models in Anti-Cancer Drug Development

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