Encapsulated human hepatocellular carcinoma cells by alginate gel beads as an in vitro metastasis model

Xu, Xiaoxi; Liu, Chang; Liu, Yang; Li, Nan; Guo, Xin; Wang, Shujun; Sun, Guangwei; Wang, Wei; Ma, Xiaojun

doi:10.1016/j.yexcr.2013.05.013

Cited by 39 publications

(54 citation statements)

References 47 publications

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“…The cell accumulation is increased over the time in cell-alginate beads (Fischbach et al 2007;Xu et al 2013). In our studies, the development of cell-aggregates within the alginate beads was confirmed.…”

Section: Discussionsupporting

confidence: 75%

“…The microscopic investigations and histological sections visualized cells aggregated with increased size from day 14. However, cell-aggregates (\ 10 4 lm 3 ) showed already an amplified size from day 3 onwards (Xu et al 2013). These are necrotic and apoptotic niches located in the center of tumors (Cassidy et al 1996).…”

Section: Discussionmentioning

confidence: 98%

“…Three dimensional cell cultures enable the mimic of in vivo conditions. Especially, cells embedded in sodium alginate display a suitable source for this investigations (Kumachev et al 2011;Pampaloni et al 2007;Xu et al 2013). The manual manufacturing is an established process in research (Jonitz et al 2011b;Fischbach et al 2009).…”

Section: Discussionmentioning

confidence: 99%

“…The stagnation and reduction of the proliferation seems to be associated with increased compactness and size of cell aggregates in the beads, which reflects in vivo tumor tissue. Additionally, the reduction of the proliferation rates can be explained by the development of cell-aggregates and proliferation resistance caused by limited space in the beads (Xu et al 2013). Furthermore, the reduced cell growth is also combined with the accumulation of metabolic end products and hypoxia within three dimensional cell culture systems (Malda et al 2007;Jonitz et al 2011a).…”

Section: Discussionmentioning

confidence: 99%

“…The difference of the toxicity was evaluated through the detection of adenylate kinases released by the damaged plasma membrane of dead cells using a high throughput screening system. However normally, the live/dead assay in combination with fluorescence microscopy is used for the differentiation of living and death cells and visualisation of toxicity (Xu et al 2013). Certainly, the quantification of the cytotoxicity by the bioscreening of cells in alginate beads is not a common screening form but could improve the investigations in a high throughput manner.…”

Section: Discussionmentioning

confidence: 99%

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3 dimensional cell cultures: a comparison between manually and automatically produced alginate beads

et al. 2015

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Cancer diseases are a common problem of the population caused by age and increased harmful environmental influences. Herein, new therapeutic strategies and compound screenings are necessary. The regular 2D cultivation has to be replaced by three dimensional cell culturing (3D) for better simulation of in vivo conditions. The 3D cultivation with alginate matrix is an appropriate method for encapsulate cells to form cancer constructs. The automated manufacturing of alginate beads might be an ultimate method for large-scaled manufacturing constructs similar to cancer tissue. The aim of this study was the integration of full automated systems for the production, cultivation and screening of 3D cell cultures. We compared the automated methods with the regular manual processes. Furthermore, we investigated the influence of antibiotics on these 3D cell culture systems. The alginate beads were formed by automated and manual procedures. The automated steps were processes by the Biomek Ò Cell Workstation (celisca, Rostock, Germany). The proliferation and toxicity were manually and automatically evaluated at day 14 and 35 of cultivation. The results visualized an accumulation and expansion of cell aggregates over the period of incubation. However, the proliferation and toxicity were faintly and partly significantly decreased on day 35 compared to day 14. The comparison of the manual and automated methods displayed similar results. We conclude that the manual production process could be replaced by the automation. Using automation, 3D cell cultures can be produced in industrial scale and improve the drug development and screening to treat serious illnesses like cancer.

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Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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3 dimensional cell cultures: a comparison between manually and automatically produced alginate beads

et al. 2015

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Fabrication of a tunable hydrogel membrane for constructing indirect cell coculture system

Song

Zheng

Zhang

et al. 2015

J of Applied Polymer Sci

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In this study, an improved indirect cell coculture system was constructed by using a polyelectrolyte complex membrane generated by alginate (A) and chitosan (C). Methodologies of characterizing thickness and permeability of flat AC membrane were first established due to the importance of these two parameters in determining intercellular distance and degree of contact between cocultured cells. Compared to reaction time, both alginate concentration and molecular weight (Mw) of chitosan play more dominant roles in determining the membrane thickness and diffusion coefficients. Moreover, cells in the alginate gel and on the AC membrane could maintain high cell viability. Thus, an improved indirect cell coculture system constructed by flat AC membrane was fabricated and characterized, which provides a robust tool to study the effect of intercellular distance and degree of contact between cocultured cells on cell–cell interactions. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43100.

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Preparation and optimization of calcium pectate beads for cell encapsulation

Zhao

Zhang

Liu

et al. 2017

J of Applied Polymer Sci

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A variety of natural polymers are considered suitable for cell entrapment. Pectin, a natural polysaccharide found in the cell walls of all higher terrestrial plants, presents great potential for cell encapsulation because of its ability to form gels. In this study, we investigated the influences of intrinsic and extrinsic factors on the formation and properties of calcium pectate (CP). Beads of CP prepared with 30-35% methyl esterification presented improved gel properties. The molecular weight (M w ), calcium content, and gel time did not significantly affect the gel properties. The gelling properties, sphericity factor (SF), and swelling ratio were significantly influenced by the degree of methyl esterification (DE) and pectin concentration. The DE (<40%), M w , and calcium concentration had negative effects on the SFs of CP beads. Moreover, increases in the DE (<40%) and pectin concentration increased the swelling ratio. The C3A cells encapsulated in optimized CP beads maintained good viability and proliferation for up to 2 weeks. In conclusion, CP beads are a potential encapsulation material for cell immobilization and application in related fields. V C 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 45685.

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Encapsulated human hepatocellular carcinoma cells by alginate gel beads as an in vitro metastasis model

Cited by 39 publications

References 47 publications

3 dimensional cell cultures: a comparison between manually and automatically produced alginate beads

3 dimensional cell cultures: a comparison between manually and automatically produced alginate beads

Fabrication of a tunable hydrogel membrane for constructing indirect cell coculture system

Preparation and optimization of calcium pectate beads for cell encapsulation

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