The Use of 3-D Cultures for High-Throughput Screening: The Multicellular Spheroid Model
By Leoni A. Kunz-Schughart, J. Freyer, F. Hofstaedter, R. Ebner. Journal of biomolecular screening, 2004
794 citations recorded by the source corpus.
Over the past few years, establishment and adaptation of cell-based assays for drug development and testing has become an important topic in high-throughput screening (HTS). Most new assays are designed to rapidly detect specific cellular effects reflecting action at various targets. However, although more complex than cell-free biochemical test systems, HTS assays using monolayer or suspension cultures still reflect a highly artificial cellular environment and may thus have limited predictive value for the clinical efficacy of a compound. Today’s strategies for drug discovery and development, be they hypothesis free or mechanism based, require facile, HTS-amenable test systems that mimic the human tissue environment with increasing accuracy in order to optimize preclinical and preanimal selection of the most active molecules from a large pool of potential effectors, for example, against solid tumors. Indeed, it is recognized that 3-dimensional cell culture systems better reflect the in vivo behavior of most cell types. However, these 3-D test systems have not yet been incorporated into mainstream drug development operations. This article addresses the relevance and potential of 3-D in vitro systems for drug development, with a focus on screening for novel antitumor drugs. Examples of 3-D cell models used in cancer research are given, and the advantages and limitations of these systems of intermediate complexity are discussed in comparison with both 2-D culture and in vivo models. The most commonly used 3-D cell culture systems, multicellular spheroids, are emphasized due to their advantages and potential for rapid development as HTS systems. Thus, multicellular tumor spheroids are an ideal basis for the next step in creating HTS assays, which are predictive of in vivo antitumor efficacy.
Subfields: Aerospace Engineering, Materials Chemistry, Radiation
View Paper: https://www.semanticscholar.org/paper/0b366d27e16e869b29c57c52880c20f9af4130f5
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Citations in the corpus
- Organ printing: Tissue spheroids as building blocks (2009, methodology): “Tissue spheroids have been used as an in vitro 3D model system in biomedical and tumor research for several decades [40–43].”
- Opportunities and Challenges for use of Tumor Spheroids as Models to Test Drug Delivery and Efficacy (2012, positive): “Spheroids with diameters larger than 400–500 μm commonly follow a concentrically layered structure consisting of a necrotic core surrounded by a viable layer of quiescent cells and an outer rim of proliferating cells [15, 16].”
- Modeling tissue morphogenesis and cancer in 3D. (2007, positive): “Homogeneous populations of spheroids may prove valuable for high-throughput drug screening (Kunz-Schughart et al., 2004).”
- Spheroid-based drug screen: considerations and practical approach (2009, background): “Hollow-fiber-based approaches and ex vivo cultures of pieces or slices from tumors are also to be mentioned as advanced 3D culture systems but are not yet sufficiently well standardized and/or depend on the supply of primary tumor tissue, which can be challenging to obtain and limits routine appli”
- Advances in establishment and analysis of three-dimensional tumor spheroid-based functional assays for target validation and drug evaluation (2012, background): “To model solid tumors more effectively, several three-dimensional culture systems have been established: whole perfused organs, tissue explants, scaffold/microcarrier-based cultures, hollow-fiber bioreactors, organotypic cultures (multicellular spheroids and cellular multilayers) and gel/matrix-base”
- Organoid-on-a-chip and body-on-a-chip systems for drug screening and disease modeling (2016, background): “Traditional in vitro 2D cultures (the norm for early-stage drug compound screening) fail to recapitulate the 3D microenvironment of in vivo tissues [3,4].”
- Recent advances in three‐dimensional multicellular spheroid culture for biomedical research (2008, background): “These properties make the MCSbased assay more predictive of in vivo therapeutic efficacy (reviewed in [26–28]).”