Special Issue "Advantages of Three Dimensional (3D) Cell Cultures"

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A special issue of Microarrays (ISSN 2076-3905).

Deadline for manuscript submissions: closed (30 June 2015)

Special Issue Editors

Guest Editor
Dr. Mohammad Reza Lornejad-Schäfer

zet - BioMed-zet Life Science GmbH, Industriezeile 36/I, A-4020 Linz, Austria
Website | E-Mail
Fax: +43 770325213
Interests: three-dimensional (3D) cell culture; in vitro models; gene expression; microarray
Guest Editor
Dr. Christine Schäfer

zet - BioMed-zet Life Science GmbH, Industriezeile 36/I, A-4020 Linz, Austria
Website | E-Mail

Special Issue Information

Dear Colleagues,

In the last years progress has been made that the common technique where adherent cells grow in monolayers in two-dimensional (2D) cell culture has its limitations. When cultured in the long-term in 2D, the supply of nutrients is insufficient, the cell-cell and cell-material interactions are unphysiological and most of the cells will not stay viable. The upcoming three-dimensional (3D) cell culture models promise to overcome these disadvantages and should resemble more likely the in vivo situation of tissues or organs. Currently, many different 3D cell culture models using different cell types, conditions and materials are under investigation. All of them is common that they must improve their advantages for basic and applied research. Microarrays can be important tools to analyze the characteristic gene expression profiles of the 3D cell culture models, doing comparative studies, and to define the 3D culture effects. The special issue invites contributions to publish their results about gene expression profiling in different 3D cell culture models.

It will be of interest to the readers of this special issue to show, how 3D cell culture has influence on cell proliferation, cell differentiation, cell viability, general cell functionality, response to stimuli and in metabolism in comparison to highlight its advantages for basic and applied research.

Dr. Mohammad Reza Lornejad-Schafer
Dr. Christine Schäfer
Guest Editors

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Microarrays is an international peer-reviewed Open Access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 300 CHF (Swiss Francs). English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections.


Keywords

  • gene expression
  • microrray
  • three-dimensional (3D) cell culture
  • two-dimensional (2D) cell culture
  • in vitro model

Published Papers (3 papers)

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Research

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Open AccessArticle Hydrogel Microwell Arrays Allow the Assessment of Protease-Associated Enhancement of Cancer Cell Aggregation and Survival
Microarrays 2013, 2(3), 208-227; doi:10.3390/microarrays2030208
Received: 2 July 2013 / Revised: 31 July 2013 / Accepted: 13 August 2013 / Published: 22 August 2013
Cited by 3 | PDF Full-text (994 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Current routine cell culture techniques are only poorly suited to capture the physiological complexity of tumor microenvironments, wherein tumor cell function is affected by intricate three-dimensional (3D), integrin-dependent cell-cell and cell-extracellular matrix (ECM) interactions. 3D cell cultures allow the investigation of cancer-associated proteases
[...] Read more.
Current routine cell culture techniques are only poorly suited to capture the physiological complexity of tumor microenvironments, wherein tumor cell function is affected by intricate three-dimensional (3D), integrin-dependent cell-cell and cell-extracellular matrix (ECM) interactions. 3D cell cultures allow the investigation of cancer-associated proteases like kallikreins as they degrade ECM proteins and alter integrin signaling, promoting malignant cell behaviors. Here, we employed a hydrogel microwell array platform to probe using a high-throughput mode how ovarian cancer cell aggregates of defined size form and survive in response to the expression of kallikreins and treatment with paclitaxel, by performing microscopic, quantitative image, gene and protein analyses dependent on the varying microwell and aggregate sizes. Paclitaxel treatment increased aggregate formation and survival of kallikrein-expressing cancer cells and levels of integrins and integrin-related factors. Cancer cell aggregate formation was improved with increasing aggregate size, thereby reducing cell death and enhancing integrin expression upon paclitaxel treatment. Therefore, hydrogel microwell arrays are a powerful tool to screen the viability of cancer cell aggregates upon modulation of protease expression, integrin engagement and anti-cancer treatment providing a micro-scaled yet high-throughput technique to assess malignant progression and drug-resistance. Full article
(This article belongs to the Special Issue Advantages of Three Dimensional (3D) Cell Cultures)

Review

Jump to: Research

Open AccessReview 3D Cell Culture in Alginate Hydrogels
Microarrays 2015, 4(2), 133-161; doi:10.3390/microarrays4020133
Received: 31 January 2015 / Revised: 16 March 2015 / Accepted: 17 March 2015 / Published: 24 March 2015
Cited by 3 | PDF Full-text (1584 KB) | HTML Full-text | XML Full-text
Abstract
This review compiles information regarding the use of alginate, and in particular alginate hydrogels, in culturing cells in 3D. Knowledge of alginate chemical structure and functionality are shown to be important parameters in design of alginate-based matrices for cell culture. Gel elasticity as
[...] Read more.
This review compiles information regarding the use of alginate, and in particular alginate hydrogels, in culturing cells in 3D. Knowledge of alginate chemical structure and functionality are shown to be important parameters in design of alginate-based matrices for cell culture. Gel elasticity as well as hydrogel stability can be impacted by the type of alginate used, its concentration, the choice of gelation technique (ionic or covalent), and divalent cation chosen as the gel inducing ion. The use of peptide-coupled alginate can control cell–matrix interactions. Gelation of alginate with concomitant immobilization of cells can take various forms. Droplets or beads have been utilized since the 1980s for immobilizing cells. Newer matrices such as macroporous scaffolds are now entering the 3D cell culture product market. Finally, delayed gelling, injectable, alginate systems show utility in the translation of in vitro cell culture to in vivo tissue engineering applications. Alginate has a history and a future in 3D cell culture. Historically, cells were encapsulated in alginate droplets cross-linked with calcium for the development of artificial organs. Now, several commercial products based on alginate are being used as 3D cell culture systems that also demonstrate the possibility of replacing or regenerating tissue. Full article
(This article belongs to the Special Issue Advantages of Three Dimensional (3D) Cell Cultures)
Open AccessReview 3D Cultivation Techniques for Primary Human Hepatocytes
Microarrays 2015, 4(1), 64-83; doi:10.3390/microarrays4010064
Received: 15 December 2014 / Revised: 8 January 2015 / Accepted: 3 February 2015 / Published: 16 February 2015
Cited by 2 | PDF Full-text (886 KB) | HTML Full-text | XML Full-text
Abstract
One of the main challenges in drug development is the prediction of in vivo toxicity based on in vitro data. The standard cultivation system for primary human hepatocytes is based on monolayer cultures, even if it is known that these conditions result in
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One of the main challenges in drug development is the prediction of in vivo toxicity based on in vitro data. The standard cultivation system for primary human hepatocytes is based on monolayer cultures, even if it is known that these conditions result in a loss of hepatocyte morphology and of liver-specific functions, such as drug-metabolizing enzymes and transporters. As it has been demonstrated that hepatocytes embedded between two sheets of collagen maintain their function, various hydrogels and scaffolds for the 3D cultivation of hepatocytes have been developed. To further improve or maintain hepatic functions, 3D cultivation has been combined with perfusion. In this manuscript, we discuss the benefits and drawbacks of different 3D microfluidic devices. For most systems that are currently available, the main issues are the requirement of large cell numbers, the low throughput, and expensive equipment, which render these devices unattractive for research and the drug-developing industry. A higher acceptance of these devices could be achieved by their simplification and their compatibility with high-throughput, as both aspects are of major importance for a user-friendly device. Full article
(This article belongs to the Special Issue Advantages of Three Dimensional (3D) Cell Cultures)

Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Type of Paper: Article
Title:
3D-Cell Culture System in Tumor Biology and Drug Screening in Due Consideration of the Microenvironment
Author:
Gerhard Unteregger *
Affiliation: University of the Saar, Clinic of Urology, Homburg7Saar, Germany; E-Mail: Gerhard.Unteregger@uniklinikum-saarland.de
Abstract:
"Good bye flat cell biology" claims for three-dimensional experimental designs in cell culture to mimic heterologeous cell-cell and cell-matrix interaction. Since the discovery in the late 70th that fibroblasts and extracellular matrix are indispensable components to build up reliable in vitro skin equivalents the necessity to include the environment in the experimental design is well acknowledged even in tumor biology. Tumour-associated and activated Fibroblasts, extracellular matrix and secreted proteins define in a well balanced communication and interaction tissue and organ development. The meaning of the surrounding environment in prostate cancer initiation and -progression was first described more than 20 years ago. During the last decades the general meaning of especially tumor-associated fibroblasts in tumor biology in several entities like breast, lung and bladder cancer was confirmed. Any genetic or epigenetic changes in these partners lead to functional changes which finally dictate the malignant process - even during patients relapse. Thus, standard monolayer cell cultures represent reduced models in epithelial cancer because they lack 3D architecture, cell-ECM interaction and fail to simulate paracrine mechanisms. One pivotal goal of in vitro studies in tumor biology and medicine is to reveal new therapeutic targets even under consideration of the surrounding environment to evaluate the efficacy of drug application and finally to disclose the molecular mechanism leading to drug resistance. Consequently, several strategies were developed to overcome the limitations of monolayer cell culture and to produce reliable, in vivo like and screening-compatible homo- and heterologeous 3D-tumor cultures to close the gap between in vitro systems and animal models. We focused our strategy on 3D- models on prostate cancer, bladder cancer and renal cell carcinoma cell lines. To build up the biological situation we combined tumor cells with tumor associated fibroblast to produce 3D-spheroids on standard 96-well plates. To avoid harvesting of spheroids for confocal microscopy we used standard assays to quantify cell growth and death. Using this approach we investigated the impact of nanomodified Zoledronic acid on 3D-spheroids from prostate carcinoma cells. Our results confirmed the assumption that there are remarkable differences in the efficacy of the drug in 3D-spheres compared to the flat cell system. Additionally, using patients derived primary prostate cancer specimens we established and 3D-invasion system to collect invasive growing tumor cells. Our results offer remarkable constant genetic imbalance only in the invasive growing 3D-spheres by CGH-analysis. In summary, 3D-cell culture technology offers an innovative powerful tool in cancer research.

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