The 3D Cell Culture System in the Study of Tumor-Applications and Prospects (original) (raw)
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3D Cell Culture Systems: Tumor Application, Advantages, and Disadvantages
International Journal of Molecular Sciences
The traditional two-dimensional (2D) in vitro cell culture system (on a flat support) has long been used in cancer research. However, this system cannot be fully translated into clinical trials to ideally represent physiological conditions. This culture cannot mimic the natural tumor microenvironment due to the lack of cellular communication (cell-cell) and interaction (cell-cell and cell-matrix). To overcome these limitations, three-dimensional (3D) culture systems are increasingly developed in research and have become essential for tumor research, tissue engineering, and basic biology research. 3D culture has received much attention in the field of biomedicine due to its ability to mimic tissue structure and function. The 3D matrix presents a highly dynamic framework where its components are deposited, degraded, or modified to delineate functions and provide a platform where cells attach to perform their specific functions, including adhesion, proliferation, communication, and apo...
Three-Dimensional Cell Culture at the Frontiers of in Vitro Cancer Research: Present Perspectives
Annals of dentistry, 2016
In recent years, three-dimensional (3D) in vitro cell culture models have earned great attention, especially in the field of human cancer disease modelling research as they provide a promising alternative towards the conventional two-dimensional (2D) monolayer culture of cells with improved tissue organization. In 2D cell culture systems, the complexity of cells on a planar surface does not accurately reflects the in vivo cellular microenvironment. Cells propagated in 3D cell culture model, on the other hand, exhibit physiologically relevant cell-to-cell interactions and cell-to-extracellular matrix (ECM) interactions, important in maintaining a normal homeostasis and specificity of tissues. This review gives an overview on 2D models and their limitations, followed by 3D cell culture models, their advantages, drawbacks and challenges in present perspectives. The review also highlights the dissimilarities of 2D and 3D models and the applicability of 3D models in current cancer research.
In Vitro 3D Cultures to Model the Tumor Microenvironment
Cancers
It is now well established that the tumor microenvironment plays a key role in determining cancer growth, metastasis and drug resistance. Thus, it is fundamental to understand how cancer cells interact and communicate with their stroma and how this crosstalk regulates disease initiation and progression. In this setting, 3D cell cultures have gained a lot of interest in the last two decades, due to their ability to better recapitulate the complexity of tumor microenvironment and therefore to bridge the gap between 2D monolayers and animal models. Herein, we present an overview of the 3D systems commonly used for studying tumor–stroma interactions, with a focus on recent advances in cancer modeling and drug discovery and testing.
Cancers
Today, innovative three-dimensional (3D) cell culture models have been proposed as viable and biomimetic alternatives for initial drug screening, allowing the improvement of the efficiency of drug development. These models are gaining popularity, given their ability to reproduce key aspects of the tumor microenvironment, concerning the 3D tumor architecture as well as the interactions of tumor cells with the extracellular matrix and surrounding non-tumor cells. The development of accurate 3D models may become beneficial to decrease the use of laboratory animals in scientific research, in accordance with the European Union’s regulation on the 3R rule (Replacement, Reduction, Refinement). This review focuses on the impact of 3D cell culture models on cancer research, discussing their advantages, limitations, and compatibility with high-throughput screenings and automated systems. An insight is also given on the adequacy of the available readouts for the interpretation of the data obta...
3D tumour models: novel in vitro approaches to cancer studies
Journal of Cell Communication and Signaling, 2011
3D in vitro models have been used in cancer research as a compromise between 2-dimensional cultures of isolated cancer cells and the manufactured complexity of xenografts of human cancers in immunocompromised animal hosts. 3D models can be tailored to be biomimetic and accurately recapitulate the native in vivo scenario in which they are found. These 3D in vitro models provide an important alternative to both complex in vivo whole organism approaches, and 2D culture with its spatial limitations. Approaches to create more biomimetic 3D models of cancer include, but are not limited to, (i) providing the appropriate matrix components in a 3D configuration found in vivo, (ii) coculturing cancer cells, endothelial cells and other associated cells in a spatially relevant manner, (iii) monitoring and controlling hypoxia-to mimic levels found in native tumours and (iv) monitoring the release of angiogenic factors by cancer cells in response to hypoxia. This article aims to overview current 3D in vitro models of cancer and review strategies employed by researchers to tackle these aspects with special reference to recent promising developments, as well as the current limitations of 2D cultures and in vivo models. 3D in vitro models provide an important alternative to both complex in vivo whole organism approaches, and 2D culture with its spatial limitations. Here we review current strategies in the field of modelling cancer, with special reference to advances in complex 3D in vitro models.
Applications and Utility of Three-Dimensional In Vitro Cell Culture for Therapeutics
Future Pharmacology
The field of 3D cell culture and its applications is rooted in the understanding of cell biology, tissue engineering, tissue morphology, disease mechanisms, and drug action. For many years, traditional 2D cell culture systems have been widely used but have proven to be limited in their ability to accurately replicate the complex microenvironment of tissues. This often results in issues with cell proliferation, aggregation, and differentiation. 3D cell culture systems have emerged as a solution to this problem and have demonstrated a more accurate simulation of in vivo physiology. This has had a major impact on drug discovery and includes the use of spheroids, organoids, scaffolds, hydrogels, and organs. This review has addressed fundamental questions and exploited utility in 3D in vitro mode of cell culture in view of therapeutics.
This study systematically investigated the cell proliferation rates, spheroid structures, cellular responses to different anti-cancer drugs, the expression of drug action-related proteins, and the possible correlations among these properties of 3D spheroids on Matrigel in comparison to 2D monolayer cells, using two cancer cell lines-the prostate cancer cell line, DU145, and the oral cancer cell line, CAL27. Compared to the traditional 2D-cultured cells, 3D-cultured CAL27 cells had enhanced proliferation by approximately 50-70% at various seeding cell densities, whereas 3D-cultured DU145 cells showed reduced proliferation at all tested seeding cell densities by 20-40%. In drug tests, the sensitivity of 3D-cultured DU145 cells relative to 2D-cultured cells showed an obvious drug action mechanism dependency in response to three anticancer drugs, Rapamycin, Docetaxel, and Camptothecin, whereas 3D-cultured CAL27 cells responded more sensitively than 2D-cultured cells to all three tested drugs, Docetaxel, Bleomycin, and Erlotinib, indicating the relative proliferation rate between 3D and 2D cultured cells may be a dominating factor in this case and mitigated the factor of drug action mechanism. The elevated expression of EGFR in 3D-cultured CAL27 was correlated with its more sensitive response to Erlotinib (acting through binding to EGRF) compared to 2D-cultured cells; Similarly, the expression of βIII tubulin in 3D-cultured DU145 cells was found to be increased and correlated with their higher resistance to Doxetaxel compared to 2D-cultured cells.
Cells
Cancer is a disorder characterized by an uncontrollable overgrowth and a fast-moving spread of cells from a localized tissue to multiple organs of the body, reaching a metastatic state. Throughout years, complexity of cancer progression and invasion, high prevalence and incidence, as well as the high rise in treatment failure cases leading to a poor patient prognosis accounted for continuous experimental investigations on animals and cellular models, mainly with 2D- and 3D-cell culture. Nowadays, these research models are considered a main asset to reflect the physiological events in many cancer types in terms of cellular characteristics and features, replication and metastatic mechanisms, metabolic pathways, biomarkers expression, and chemotherapeutic agent resistance. In practice, based on research perspective and hypothesis, scientists aim to choose the best model to approach their understanding and to prove their hypothesis. Recently, 3D-cell models are seen to be highly incorpo...
Current pharmaceutical design, 2018
In vitro tests allow establishing experimental variables. However, in vitro results cannot be extrapolated to in vivo tests. Considering that three-dimensional (3D) culture has been one of the best ways to portray the in vivo system of most cell types, it is possible to carry out assays with a great clinical relevance for the analysis of the screening, action and resistance of antitumor drugs. Thus, the objective of the present study was to compare between 2D and 3D cell culture forms to conclude which is the most suitable model for preclinical in vitro drug testing. We evaluated the proliferation, genetic expression and chemoresistance of prostate tumor cell lines, PC-3, LNCaP and DU145. Prostate tumor cell lines PC-3, LNCaP and DU145 were treated with the antineoplastic drugs paclitaxel and docetaxel and evaluated with cytotoxicity, cell proliferation and gene expression assays in 2D and magnetic 3D bioprinting cultures. Lower cell proliferation rate, more resistance to paclitaxel...
Three-Dimensional (3D) in vitro cell culture protocols to enhance glioblastoma research
PLOS ONE
Three-dimensional (3D) cell culture models can help bridge the gap between in vitro cell cultures and in vivo responses by more accurately simulating the natural in vivo environment, shape, tissue stiffness, stressors, gradients and cellular response while avoiding the costs and ethical concerns associated with animal models. The inclusion of the third dimension in 3D cell culture influences the spatial organization of cell surface receptors that interact with other cells and imposes physical restrictions on cells in compared to Two-dimensional (2D) cell cultures. Spheroids’ distinctive cyto-architecture mimics in vivo cellular structure, gene expression, metabolism, proliferation, oxygenation, nutrition absorption, waste excretion, and drug uptake while preserving cell–extracellular matrix (ECM) connections and communication, hence influencing molecular processes and cellular phenotypes. This protocol describes the in vitro generation of tumourspheroids using the low attachment pla...