Cited by 7983D Printing in Biomedical ResearchCancer Cells and MetastasisAnimal testing and alternatives

The DOI matches its Crossref record; 155 of the 163 references it cites were found in a registry or an index.

The use of 3-d cultures for high-throughput screening: the multicellular spheroid model.

Open access

Kunz-Schughart, Leoni A., Freyer, James P., Hofstaedter, Ferdinand, Ebner, Reinhard·2004·SLAS DISCOVERY

Open this paper in CoChat — free account Open PDF

Abstract

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.

Integrity signals

Registry

Crossref · 10.1177/1087057104265040

Cites

155 of 155 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Cell and environment interactions in tumor microregions: the multicell spheroid model.
Sutherland, R. M. (1988) · Science · doi:10.1126/science.2451290 · Cited by 1,803
Biology's new dimension
Abbott, A. (2003) · Nature · doi:10.1038/424870a · Cited by 1,228
Relationships between drug activity in NCI preclinical in vitro and in vivo models and early clinical trials
Johnson, J. I., Decker, S., Zaharevitz, D. W., Rubinstein, L., Venditti, J. M., Schepartz, S. A., Kalyandrug, S., Christian, M. C., Arbuck, S. G., Hollingshead, M. G., et al. (2001) · British Journal of Cancer · doi:10.1054/bjoc.2001.1796 · Cited by 856
The organizing principle: microenvironmental influences in the normal and malignant breast
Bissell, M. J., Radisky, D. C., Rizki, A., Weaver, V. M., & Petersen, O. W. (2002) · Differentiation · doi:10.1046/j.1432-0436.2002.700907.x · Cited by 617
Growth of Multicell Spheroids in Tissue Culture as a Model of Nodular Carcinomas 2
Sutherland, R. M., McCredie, J. A., & Inch, W. R. (1971) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/46.1.113 · Cited by 585
High-throughput screening: new technology for the 21st century
Hertzberg, R., & Pope, A. J. (2000) · Current Opinion in Chemical Biology · doi:10.1016/s1367-5931(00)00110-1 · Cited by 547
Three-dimensional cell cultures: from molecular mechanisms to clinical applications
Mueller‐Klieser, W. (1997) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1997.273.4.c1109 · Cited by 539
Untitled work
(2003) · PubMed · Cited by 523
High-throughput and ultra-high-throughput screening: solution- and cell-based approaches
Sundberg, S. (2000) · Current Opinion in Biotechnology · doi:10.1016/s0958-1669(99)00051-8 · Cited by 455
Optimized suspension culture: the rotating-wall vessel
Hammond, T. G., & Hammond, J. (2001) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.2001.281.1.f12 · Cited by 441

Show all 163 references

Research works printed but not linked: 4

Muralidhar, 2001, Development of high-density cultivation systems by bioencapsulation, Curr Sci, 81, 263
Ochs, 2003, Evidence for the isolation, growth, and characterization of malignant cells in primary cultures of human tumors, In Vitro Cell Dev Biol Anim, 39, 63, 10.1290/1543-706X(2003)039<0063:EFTIGA>2.0.CO;2 · DOI
Gottwald, 2002, Gewebezüchtung. Hilfsarbeiter für die Leber, Spektrum der Wissenschaft, 1, 44
Düchting, 1995, Modeling of radiogenic responses induced by fractionated irradiation in malignant and normal tissue, Stem Cells, 13, 301

Sorted by citations

Items 101–200 of 798

A Quadruple‐Action Platinum(IV) Prodrug with Anticancer Activity Against KRAS Mutated Cancer Cell Lines
Petruzzella, E., Braude, J. P., Aldrich-Wright, J. R., Gandin, V., & Gibson, D. (2017) · Angewandte Chemie International Edition · doi:10.1002/anie.201706739 · Cited by 121
3D tissue culture substrates produced by microthermoforming of pre-processed polymer films
Giselbrecht, S., Gietzelt, T., Gottwald, E., Trautmann, C., Truckenmüller, R. K., Weibezahn, K. F., & Welle, A. (2006) · Biomedical Microdevices · doi:10.1007/s10544-006-8174-8 · Cited by 120
Drug Discovery Approaches Utilizing Three-Dimensional Cell Culture
Ryan, S.-L., Baird, A., Vaz, G. M. F., Urquhart, A. J., Senge, M. O., Richard, D. J., O'Byrne, K. J., & Davies, A. M. (2016) · Assay and Drug Development Technologies · doi:10.1089/adt.2015.670 · Cited by 126
Scalable robotic biofabrication of tissue spheroids
Mehesz, A. N., Brown, J. L., Hajdu, Z., Beaver, W., da Silva, J. V. L., Visconti, R. P., Markwald, R. R., & Mironov, V. A. (2011) · Biofabrication · doi:10.1088/1758-5082/3/2/025002 · Cited by 119
Osteoblasts and Bone Marrow Mesenchymal Stromal Cells Control Hematopoietic Stem Cell Migration and Proliferation in 3D In Vitro Model
de Barros, A. P. D. N., Takiya, C. M., Garzoni, L. R., Leal‐Ferreira, M. L., Dutra, H. S., Chiarini, L. B., Meirelles, M. N. L., Borojević, R., & Rossi, M. I. D. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009093 · Cited by 114
A novel three-dimensional stromal-based model forin vitrochemotherapy sensitivity testing of leukemia cells
Aljitawi, O. S., Li, D., Xiao, Y., Zhang, D., Karthik, R., Stehno‐Bittel, L., Veldhuizen, P. J. V., Lin, T. L., Kambhampati, S., & Garimella, R. (2013) · Leukemia & lymphoma/Leukemia and lymphoma · doi:10.3109/10428194.2013.793323 · Cited by 113
The Impact of Simulated and Real Microgravity on Bone Cells and Mesenchymal Stem Cells
Ulbrich, C., Wehland, M., Pietsch, J., Aleshcheva, G., Wise, P. M., van Loon, J. J. W. A., Magnusson, N. E., Infanger, M., Grosse, J., Eilles, C., et al. (2014) · BioMed Research International · doi:10.1155/2014/928507 · Cited by 113
Environmental Toxin Screening Using Human-Derived 3D Bioengineered Liver and Cardiac Organoids
Forsythe, S. D., Devarasetty, M., Shupe, T., Bishop, C., Atala, A., Soker, S., & Skardal, A. (2018) · Frontiers in Public Health · doi:10.3389/fpubh.2018.00103 · Cited by 112
Imaging Mass Spectrometry of Three-Dimensional Cell Culture Systems
Li, H., & Hummon, A. B. (2011) · Analytical Chemistry · doi:10.1021/ac202356g · Cited by 112
Efficacy of anti-cancer agents in cell lines versus human primary tumour tissue
Cree, I. A., Glaysher, S., & Harvey, A. L. (2010) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2010.05.001 · Cited by 111
High-throughput generation of spheroids using magnetic nanoparticles for three-dimensional cell culture
Kim, J. A., Choi, J., Kim, M., Rhee, W. J., Son, B., Jung, H.-K., & Park, T. H. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2013.07.056 · Cited by 114
Mixed hydrogel bead-based tumor spheroid formation and anticancer drug testing
Wang, Y., & Wang, J. (2014) · The Analyst · doi:10.1039/c4an00015c · Cited by 113
Characterizing the role of monocytes in T cell cancer immunotherapy using a 3d microfluidic model
Lee, S. W. L., Adriani, G., Ceccarello, E., Pavesi, A., Tan, A. T., Bertoletti, A., Kamm, R. D., & Wong, S. C. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00416 · Cited by 109
A microfabricated platform for high-throughput unconfined compression of micropatterned biomaterial arrays
Moraes, C., Wang, G., Sun, Y., & Simmons, C. A. (2009) · Biomaterials · doi:10.1016/j.biomaterials.2009.09.068 · Cited by 108
Superhydrophobic Chips for Cell Spheroids High-Throughput Generation and Drug Screening
Oliveira, M. B., Neto, A. I., Correia, C. R., Rial-Hermida, M. I., Alvarez‐Lorenzo, C., & Mano, J. F. (2014) · ACS Applied Materials & Interfaces · doi:10.1021/am5018607 · Cited by 109
A spheroid-based 3-D culture model for pancreatic cancer drug testing, using the acid phosphatase assay
Wen, Z., Liao, Q., Hu, Y., You, L., Zhou, L., & Zhao, Y. (2013) · Brazilian Journal of Medical and Biological Research · doi:10.1590/1414-431x20132647 · Cited by 102
Scaffold-free three-dimensional cell culturing using magnetic levitation
Türker, E., Demirçak, N., & Yıldız, A. A. (2018) · Biomaterials Science · doi:10.1039/c8bm00122g · Cited by 102
Probing the relevance of 3D cancer models in nanomedicine research
Leong, D. T., & Ng, K. W. (2014) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2014.06.007 · Cited by 104
Synergistic combination chemotherapy using carrier-free celastrol and doxorubicin nanocrystals for overcoming drug resistance
Xiao, Y., Liu, J., Guo, M., Zhou, H., Jin, J., Liu, J., Liu, Y., Zhang, Z., & Chen, C. (2018) · Nanoscale · doi:10.1039/c8nr02700e · Cited by 102
Comparative Study of Multicellular Tumor Spheroid Formation Methods and Implications for Drug Screening
Gencoglu, M. F., Barney, L. E., Hall, C. L., Brooks, E. A., Schwartz, A. D., Corbett, D. C., Stevens, K. R., & Peyton, S. R. (2017) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.7b00069 · Cited by 102
Three-Dimensional Tissue Models for Drug Discovery and Toxicology
Pampaloni, F., Stelzer, E. H. K., & Masotti, A. (2009) · Recent Patents on Biotechnology · doi:10.2174/187220809788700201 · Cited by 101
Phenotypic Characterization of Toxic Compound Effects on Liver Spheroids Derived from iPSC Using Confocal Imaging and Three-Dimensional Image Analysis
Sirenko, O., Hancock, M. K., Hesley, J., Hong, D., Cohen, A., Gentry, J., Carlson, C. B., & Mann, D. A. (2016) · Assay and Drug Development Technologies · doi:10.1089/adt.2016.729 · Cited by 99
Microengineering methods for cell-based microarrays and high-throughput drug-screening applications
Xu, F., Wu, J., Wang, S., Durmus, N. G., Gurkan, U. A., & Demirci, U. (2011) · Biofabrication · doi:10.1088/1758-5082/3/3/034101 · Cited by 98
A review of manufacturing capabilities of cell spheroid generation technologies and future development
Liu, D., Chen, S., & Naing, M. W. (2020) · Biotechnology and Bioengineering · doi:10.1002/bit.27620 · Cited by 96
Phenotypic Characterization of Prostate Cancer LNCaP Cells Cultured within a Bioengineered Microenvironment
Sieh, S., Taubenberger, A. V., Rizzi, S. C., Sadowski, M. C., Lehman, M., Rockstroh, A., An, J., Clements, J. A., Nelson, C. C., & Hutmacher, D. W. (2012) · PLoS ONE · doi:10.1371/journal.pone.0040217 · Cited by 97
Micro-scaffold array chip for upgrading cell-based high-throughput drug testing to 3D using benchtop equipment
Li, X., Zhang, X., Zhao, S., Wang, J., Liu, G., & Du, Y. (2013) · Lab on a Chip · doi:10.1039/c3lc51103k · Cited by 97
Engineered Liver-Like Tissue on a Capillarized Matrix for Applied Research
Linke, K., Schanz, J., Hansmann, J., Walles, T., Brunner, H., & Mertsching, H. (2007) · Tissue Engineering · doi:10.1089/ten.2006.0388 · Cited by 91
Advanced biomaterials and microengineering technologies to recapitulate the stepwise process of cancer metastasis
Peela, N., Truong, D. D., Saini, H., Chu, H., Mashaghi, S., Ham, S. L., Singh, S. K., Tavana, H., Mosadegh, B., & Nikkhah, M. (2017) · Biomaterials · doi:10.1016/j.biomaterials.2017.04.017 · Cited by 97
Potentiation of chemotherapeutic drugs by energy metabolism inhibitors 2‐deoxyglucose and etomoxir
Hernlund, E., Ihrlund, L. S., Khan, O. M., Ateş, Y. Ö., Linder, S. T., Panaretakis, T., & Shoshan, M. C. (2008) · International Journal of Cancer · doi:10.1002/ijc.23525 · Cited by 91
Cytotoxicity and infiltration of human NK cells in in vivo-like tumor spheroids
Giannattasio, A., Weil, S., Kloeß, S., Ansari, N., Stelzer, E. H. K., Cerwenka, A., Steinle, A., Koehl, U., & Koch, J. (2015) · BMC Cancer · doi:10.1186/s12885-015-1321-y · Cited by 94
Spheroid model study comparing the biocompatibility of Biodentine and MTA
Pérard, M., Clerc, J. L., Méary, F., Pérez, F., Tricot‐Doleux, S., & Pellen‐Mussi, P. (2013) · Journal of Materials Science Materials in Medicine · doi:10.1007/s10856-013-4908-3 · Cited by 89
Cell–Cell Adhesion and Cytoskeleton Tension Oppose Each Other in Regulating Tumor Cell Aggregation
Saïas, L., Gomes, A., Cazalès, M., Ducommun, B., & Lobjois, V. (2015) · Cancer Research · doi:10.1158/0008-5472.can-14-3534 · Cited by 91
Octa-arginine-modified pegylated liposomal doxorubicin: An effective treatment strategy for non-small cell lung cancer
Biswas, S., Deshpande, P. P., Perche, F., Dodwadkar, N. S., Sane, S. D., & Torchilin, V. P. (2013) · Cancer Letters · doi:10.1016/j.canlet.2013.02.020 · Cited by 88
Sertoli cell as a model in male reproductive toxicology: Advantages and disadvantages
Reis, M. M. S., Moreira, A. C., Sousa, M., Mathur, P. P., Oliveira, P. F., & Alves, M. G. (2015) · Journal of Applied Toxicology · doi:10.1002/jat.3122 · Cited by 91
Three-Dimensional Cell Cultures in Toxicology
Pampaloni, F., & Stelzer, E. H. K. (2009) · Biotechnology and Genetic Engineering Reviews · doi:10.5661/bger-26-117 · Cited by 91
Digital Microfluidics for Automated Hanging Drop Cell Spheroid Culture
Aijian, A. P., & Garrell, R. L. (2014) · SLAS TECHNOLOGY · doi:10.1177/2211068214562002 · Cited by 88
Coordination of Hydroxyquinolines to a Ruthenium Bis-dimethyl-phenanthroline Scaffold Radically Improves Potency for Potential as Antineoplastic Agents
Heidary, D. K., Howerton, B. S., & Glazer, E. C. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm501043s · Cited by 87
Inferring Growth Control Mechanisms in Growing Multi-cellular Spheroids of NSCLC Cells from Spatial-Temporal Image Data
Jagiella, N., Müller, B., Müller, M., Vignon-Clementel, I. E., & Drasdo, D. (2016) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1004412 · Cited by 90
Continuously perfused microbubble array for 3D tumor spheroid model
Agastin, S., Giang, U.-B. T., Geng, Y., DeLouise, L. A., & King, M. R. (2011) · Biomicrofluidics · doi:10.1063/1.3596530 · Cited by 86
A microfluidic chip with a U-shaped microstructure array for multicellular spheroid formation, culturing and analysis
Fu, C.-Y., Tseng, S., Yang, S., Hsu, L., Liu, C., & Chang, H. (2014) · Biofabrication · doi:10.1088/1758-5082/6/1/015009 · Cited by 92
Drug testing on 3D in vitro tissues trapped on a microcavity chip
Kloß, D., Fischer, M., Rothermel, A., Simon, J. C., & Robitzki, A. A. (2008) · Lab on a Chip · doi:10.1039/b800394g · Cited by 86
Antimicrobial efficacy against Pseudomonas aeruginosa biofilm formation in a three-dimensional lung epithelial model and the influence of fetal bovine serum
Crabbé, A., Liu, Y., Matthijs, N., Rigole, P., de la Fuente‐Núñez, C., Davis, R. R., Ledesma, M. A., Sarker, S. F., Houdt, R. V., Hancock, R. E. W., et al. (2017) · Scientific Reports · doi:10.1038/srep43321 · Cited by 86
Emulsion technologies for multicellular tumour spheroid radiation assays
McMillan, K. S., McCluskey, A. G., Sørensen, A., Boyd, M., & Zagnoni, M. (2015) · The Analyst · doi:10.1039/c5an01382h · Cited by 89
Tumor-specific penetrating peptides-functionalized hyaluronic acid-d-α-tocopheryl succinate based nanoparticles for multi-task delivery to invasive cancers
Liang, D.-S., Su, H., Liu, Y., Wang, A.-T., & Qi, X. (2015) · Biomaterials · doi:10.1016/j.biomaterials.2015.08.035 · Cited by 85
Microfluidics as an Enabling Technology for Personalized Cancer Therapy
Mathur, L., Ballinger, M., Utharala, R., & Merten, C. A. (2019) · Small · doi:10.1002/smll.201904321 · Cited by 83
Immunocompetent cancer-on-chip models to assess immuno-oncology therapy
Maulana, T. I., Kromidas, E., Wallstabe, L., Cipriano, M., Alb, M., Zaupa, C., Hudecek, M., Fogal, B., & Loskill, P. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.03.015 · Cited by 86
Functional three‐dimensional HepG2 aggregate cultures generated from an ultrasound trap: Comparison with HepG2 spheroids
Jian, L., Kuznetsova, L. A., Edwards, G. O., Xu, J., Ma, M., Purcell, W. M., Jackson, S. K., & Coakley, W. T. (2007) · Journal of Cellular Biochemistry · doi:10.1002/jcb.21345 · Cited by 87
Cell Spheroids with Enhanced Aggressiveness to Mimic Human Liver Cancer In Vitro and In Vivo
Jung, H.-R., Kang, H. M., Ryu, J., Kim, D., Noh, K. H., Kim, E., Lee, H., Chung, K., Cho, H., Kim, N.-S., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-10828-7 · Cited by 81
Sarcoma Spheroids and Organoids—Promising Tools in the Era of Personalized Medicine
Colella, G., Fazioli, F., Gallo, M., Chiara, A. D., Apice, G., Ruosi, C., Cimmino, A., & de Nigris, F. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19020615 · Cited by 88
Functional and Mechanistic Neurotoxicity Profiling Using Human iPSC-Derived Neural 3D Cultures
Sirenko, O., Parham, F., Dea, S., Sodhi, N., Biesmans, S., Mora-Castilla, S., Ryan, K., Behl, M., Chandy, G., Crittenden, C., et al. (2018) · Toxicological Sciences · doi:10.1093/toxsci/kfy218 · Cited by 84
A Human iPSC-derived 3D platform using primary brain cancer cells to study drug development and personalized medicine
Plummer, S. M., Wallace, S., Ball, G., Lloyd, R., Schiapparelli, P. V., Quiñones‐Hinojosa, A., Härtung, T., & Pamies, D. (2019) · Scientific Reports · doi:10.1038/s41598-018-38130-0 · Cited by 85
Role of Patient-Derived Models of Cancer in Translational Oncology
Idrisova, K., Simon, H., & Gomzikova, M. O. (2022) · Cancers · doi:10.3390/cancers15010139 · Cited by 84
Modified gum arabic cross-linked gelatin scaffold for biomedical applications
Sarika, P. R., Cinthya, K., Jayakrishnan, A., Anilkumar, P. R., & James, N. R. (2014) · Materials Science and Engineering C · doi:10.1016/j.msec.2014.06.042 · Cited by 81
Microscale screening systems for 3D cellular microenvironments: platforms, advances, and challenges
Montanez-Sauri, S. I., Beebe, D. J., & Sung, K. E. (2014) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1738-5 · Cited by 81
Colorectal cancer triple co-culture spheroid model to assess the biocompatibility and anticancer properties of polymeric nanoparticles
Bauleth-Ramos, T., Feijão, T., Gonçalves, A., Shahbazi, M.-A., Liu, Z., Barrias, C., Oliveira, M. J., Granja, P., Santos, H. A., & Sarmento, B. (2020) · Journal of Controlled Release · doi:10.1016/j.jconrel.2020.04.025 · Cited by 79
Chlorin e6 and CRISPR-Cas9 dual-loading system with deep penetration for a synergistic tumoral photodynamic-immunotherapy
Yang, C., Fu, Y., Huang, C. Z., Hu, D., Zhou, K., Hao, Y., Chu, B., Yang, Y., & Qian, Z. (2020) · Biomaterials · doi:10.1016/j.biomaterials.2020.120194 · Cited by 79
Three-dimensional perfused cell culture
Li, Z., & Cui, Z. (2013) · Biotechnology Advances · doi:10.1016/j.biotechadv.2013.10.006 · Cited by 84
Shifting the Light Activation of Metallodrugs to the Red and Near-Infrared Region in Anticancer Phototherapy
Bonnet, S. A. (2014) · Comments on Inorganic Chemistry · doi:10.1080/02603594.2014.979286 · Cited by 79
Drug Discovery Goes Three-Dimensional: Goodbye to Flat High-Throughput Screening?
Eglen, R. M., & Randle, D. H. (2015) · Assay and Drug Development Technologies · doi:10.1089/adt.2015.647 · Cited by 79
Generation of uniform liver spheroids from human pluripotent stem cells for imaging-based drug toxicity analysis
Lee, G., Kim, H., Park, J. Y., Kim, G., Han, J., Chung, S. H., Yang, J. H., Jeon, J. S., Woo, D., Han, C., et al. (2020) · Biomaterials · doi:10.1016/j.biomaterials.2020.120529 · Cited by 79
Enabling screening in 3D microenvironments: probing matrix and stromal effects on the morphology and proliferation of T47D breast carcinoma cells
Montanez-Sauri, S. I., Sung, K. E., Berthier, E., & Beebe, D. J. (2013) · Integrative Biology · doi:10.1039/c3ib20225a · Cited by 80
Mesenchymal stem cells support growth and organization of host-liver colorectal-tumor organoids and possibly resistance to chemotherapy
Devarasetty, M., Wang, E. C., Söker, S., & Skardal, A. (2017) · Biofabrication · doi:10.1088/1758-5090/aa7484 · Cited by 78
Cell-based drug screening on microfluidics
Zhai, J., Yi, S., Jia, Y., Mak, P., & Martins, R. P. (2019) · TrAC Trends in Analytical Chemistry · doi:10.1016/j.trac.2019.05.018 · Cited by 75
Activity of Anticancer Agents in a Three-Dimensional Cell Culture Model
Nirmalanandhan, V. S., Duren, A., Hendricks, P., Vielhauer, G. A., & Sittampalam, G. S. (2010) · Assay and Drug Development Technologies · doi:10.1089/adt.2010.0276 · Cited by 72
In vitro and ex vivo models of human asthma
Blume, C., & Davies, D. E. (2013) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2012.12.014 · Cited by 79
Droplet-based microfluidic system to form and separate multicellular spheroids using magnetic nanoparticles
Yoon, S., Kim, J. A., Lee, S. H., Kim, M., & Park, T. H. (2013) · Lab on a Chip · doi:10.1039/c3lc41322e · Cited by 76
Generation of multicellular tumor spheroids of breast cancer cells: How to go three-dimensional
Nagelkerke, A., Bussink, J., Sweep, F. C. G. J., & Span, P. N. (2013) · Analytical Biochemistry · doi:10.1016/j.ab.2013.02.004 · Cited by 74
Recapitulating epithelial tumor microenvironment in vitro using three dimensional tri-culture of human epithelial, endothelial, and mesenchymal cells
Lamichhane, S. P., Arya, N., Kohler, E., Xiang, S., Christensen, J., & Shastri, V. P. (2016) · BMC Cancer · doi:10.1186/s12885-016-2634-1 · Cited by 79
High-Throughput Screening of Natural Products for Cancer Therapy
Harvey, A. R., & Cree, I. A. (2010) · Planta Medica · doi:10.1055/s-0030-1250162 · Cited by 73
Inkjet dispensing technologies: recent advances for novel drug discovery
Machekposhti, S. A., Mohaved, S., & Narayan, R. J. (2019) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2019.1567489 · Cited by 72
The impact of microfluidics in high-throughput drug-screening applications
Stefano, P. D., Bianchi, E., & Dubini, G. (2022) · Biomicrofluidics · doi:10.1063/5.0087294 · Cited by 77
Time-lapse 3-D measurements of a glucose biosensor in multicellular spheroids by light sheet fluorescence microscopy in commercial 96-well plates
Maioli, V., Chennell, G., Sparks, H., Lana, T., Kumar, S., Carling, D., Sardini, A., & Dunsby, C. W. (2016) · Scientific Reports · doi:10.1038/srep37777 · Cited by 72
In vitro modeling of the prostate cancer microenvironment
Ellem, S. J., De-Juan-Pardo, E. M., & Risbridger, G. P. (2014) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2014.04.008 · Cited by 68
Alginate-based microfluidic system for tumor spheroid formation and anticancer agent screening
Chen, M. C. W., Gupta, M., & Cheung, K. C. (2010) · Biomedical Microdevices · doi:10.1007/s10544-010-9417-2 · Cited by 70
Large scale production and controlled deposition of single HUVEC spheroids for bioprinting applications
Gutzweiler, L., Kartmann, S., Tröndle, K., Benning, L., Finkenzeller, G., Zengerle, R., Koltay, P., Stark, G. B., & Zimmermann, S. (2017) · Biofabrication · doi:10.1088/1758-5090/aa7218 · Cited by 71
Spheroid-based 3D Cell Cultures Enable Personalized Therapy Testing and Drug Discovery in Head and Neck Cancer
Hagemann, J., JACOBI, C., Hahn, M., Schmid, V., Welz, C., Schwenk‐Zieger, S., Stauber, R. H., Baumeister, P., & Becker, S. (2017) · Anticancer Research · doi:10.21873/anticanres.11555 · Cited by 73
Therapeutic potential of the phosphino Cu(I) complex (HydroCuP) in the treatment of solid tumors
Gandin, V., Ceresa, C., Esposito, G., Indraccolo, S., Porchia, M., Tisato, F., Santini, C., Pellei, M., & Marzano, C. (2017) · Scientific Reports · doi:10.1038/s41598-017-13698-1 · Cited by 70
Recommended guidelines for developing, qualifying, and implementing complex in vitro models (CIVMs) for drug discovery
Ekert, J. E., Deakyne, J., Pribul-Allen, P., Terry, R., Schofield, C., Jeong, C. G., Storey, J., Mohamet, L., Francis, J., Naidoo, A., et al. (2020) · SLAS DISCOVERY · doi:10.1177/2472555220923332 · Cited by 68
Alginate core-shell beads for simplified three-dimensional tumor spheroid culture and drug screening
Yu, L., Ni, C., Grist, S. M., Bayly, C. L., & Cheung, K. C. (2015) · Biomedical Microdevices · doi:10.1007/s10544-014-9918-5 · Cited by 70
Three-dimensional polymer scaffolds for high throughput cell-based assay systems
Cheng, K., Lai, Y., & Kisaalita, W. S. (2008) · Biomaterials · doi:10.1016/j.biomaterials.2008.03.015 · Cited by 71
High-throughput fluorescence imaging approaches for drug discovery usingin vitroandin vivothree-dimensional models
Martinez, N. J., Titus, S. A., Wagner, A. K., & Simeonov, A. M. (2015) · Expert Opinion on Drug Discovery · doi:10.1517/17460441.2015.1091814 · Cited by 68
Diffusion-mediated in situ alginate encapsulation of cell spheroids using microscale concave well and nanoporous membrane
Lee, K. H., No, D. Y., Kim, S., Ryoo, J.-H., Wong, S. F., & Lee, S. (2011) · Lab on a Chip · doi:10.1039/c0lc00540a · Cited by 68
Multi-functional nanoparticles as theranostic agents for the treatment & imaging of pancreatic cancer
Chakka, L. R. J., Chellappan, D. R., Bhavsar, D. V., Ranganathan, R., Banudevi, S., Subramanian, A., Sharma, U., Jagannathan, N. R., Krishnan, U. M., & Sethuraman, S. (2016) · Acta Biomaterialia · doi:10.1016/j.actbio.2016.11.053 · Cited by 68
Multiscale image analysis reveals structural heterogeneity of the cell microenvironment in homotypic spheroids
Schmitz, A., Fischer, S., Mattheyer, C., Pampaloni, F., & Stelzer, E. H. K. (2017) · Scientific Reports · doi:10.1038/srep43693 · Cited by 71
Three-dimensional polymeric systems for cancer cell studies
Xu, F., & Burg, K. J. L. (2007) · Cytotechnology · doi:10.1007/s10616-007-9065-4 · Cited by 67
Three-dimensional modelling of ovarian cancer: from cell lines to organoids for discovery and personalized medicine
Yee, C., Dickson, K.-A., Muntasir, M. N., Ma, Y., & Marsh, D. J. (2022) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2022.836984 · Cited by 66
Applications and Advances of Multicellular Tumor Spheroids: Challenges in Their Development and Analysis
Mitrakas, A. G., Tsolou, A., Didaskalou, S., Karkaletsou, L., Efstathiou, C., Eftalitsidis, E., Marmanis, K., & Koffa, M. D. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24086949 · Cited by 65
Prediction of individual response to anticancer therapy: historical and future perspectives
Unger, F. T., Witte, I., & David, K. A. (2014) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1772-3 · Cited by 71
Translation of a Tumor Microenvironment Mimicking 3D Tumor Growth Co-culture Assay Platform to High-Content Screening
Krausz, E., Hoogt, R. D., Gustin, E. M., Cornelissen, F. W., Grand‐Perret, T., Janssen, L., Vloemans, N., Wuyts, D., Frans, S., Axel, A. E., et al. (2012) · SLAS DISCOVERY · doi:10.1177/1087057112456874 · Cited by 65
Stem Cells in Drug Discovery, Tissue Engineering, and Regenerative Medicine: Emerging Opportunities and Challenges
Nirmalanandhan, V., & Sittampalam, G. (2009) · Journal of biomolecular screening · doi:10.1177/1087057109336591 · Cited by 79
Enhancement of human adipose-derived stem cell spheroid differentiation in an in situ enzyme-crosslinked gelatin hydrogel
Tsai, C.-C., Hong, Y.-J., Lee, R. J., Cheng, N., & Yu, J. (2018) · Journal of Materials Chemistry B · doi:10.1039/c8tb02835d · Cited by 65
α2-Macroglobulin Inhibits the Malignant Properties of Astrocytoma Cells by Impeding β-Catenin Signaling
Lindner, I., Hemdan, N. Y. A., Buchold, M., Huse, K., Bigl, M., Oerlecke, I., Ricken, A. M., Gaunitz, F., Sack, U., Naumann, A., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-09-1462 · Cited by 64
Therapeutic potential of targeted multifunctional nanocomplex co-delivery of siRNA and low-dose doxorubicin in breast cancer
Dong, D., Gao, W., Liu, Y., & Qi, X. (2015) · Cancer Letters · doi:10.1016/j.canlet.2015.01.011 · Cited by 63
Electrical Impedance Spectroscopy for Microtissue Spheroid Analysis in Hanging-Drop Networks
Schmid, Y. R. F., Bürgel, S. C., Misun, P. M., Hierlemann, A. R., & Frey, O. (2016) · ACS Sensors · doi:10.1021/acssensors.6b00272 · Cited by 63
Three-dimensional digital microfluidic manipulation of droplets in oil medium
Hong, J., Kim, Y. K., Won, D., Kim, J., & Lee, S. J. (2015) · Scientific Reports · doi:10.1038/srep10685 · Cited by 66
Digital Twins for Tissue Culture Techniques—Concepts, Expectations, and State of the Art
Möller, J., & Pörtner, R. (2021) · Processes · doi:10.3390/pr9030447 · Cited by 63
Engineered 3D environments to elucidate the effect of environmental parameters on drug response in cancer
Håkanson, M., Textor, M., & Charnley, M. (2010) · Integrative Biology · doi:10.1039/c0ib00074d · Cited by 62
mTOR Mediates Survival Signals in Malignant Mesothelioma Grown as Tumor Fragment Spheroids
Wilson, S. M., Barbone, D., Yang, T., Jablons, D. M., Bueno, R., Sugarbaker, D. J., Nishimura, S. L., Gordon, G. J., & Broaddus, V. C. (2008) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2007-0460oc · Cited by 62
Neuronal gene delivery by negatively charged pullulan–spermine/DNA anioplexes
Thakor, D. K., Teng, Y. D., & Tabata, Y. (2009) · Biomaterials · doi:10.1016/j.biomaterials.2008.12.032 · Cited by 61
Flow Cytometry: Impact on Early Drug Discovery
Edwards, B. S., & Sklar, L. A. (2015) · SLAS DISCOVERY · doi:10.1177/1087057115578273 · Cited by 65

Authors: Kunz-Schughart, L. A., Freyer, J. P., Hofstaedter, F., & Ebner, R.
Affiliations: Los Alamos National Laboratory (US)
University of Regensburg (DE)
Avalon Pharma (United States) (US)
Venue: SLAS DISCOVERY
Publisher: Elsevier BV
Published: 2004-06
Volume: 9
Issue: 4
Pages: 273-285
ISSN: 2472-5552 (ISSN-L)
DOI: 10.1177/1087057104265040
OpenAlex: W2140723257
Cited by: 797
References: 163
Citations by year: 2026: 21 · 2025: 26 · 2024: 24 · 2023: 29 · 2022: 38 · 2021: 38 · 2020: 45 · 2019: 39 · 2018: 51 · 2017: 61 · 2016: 63 · 2015: 50 · 2014: 46 · 2013: 58 · 2012: 29
FWCI: 11.64
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by-nc-nd/4.0/ (vor, 6538 d)
Locations: SLAS DISCOVERY (publishedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
University of Regensburg Publication Server (University of Regensburg) (submittedVersion)
Topics: Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Health Sciences › Veterinary › Small Animals › Animal testing and alternatives
Keywords: tumor spheroids, 3D cell culture, high-throughput screening, anticancer drug screening, drug development, solid tumors, cell-based assays
MeSH terms: Animals, Antineoplastic Agents, Drug Evaluation, Preclinical, Drug Screening Assays, Antitumor, Humans, Models, Biological, Tumor Cells, Cultured, Spheroids, Cellular, In Vitro Techniques

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

The use of 3-d cultures for high-throughput screening: the multicellular spheroid model.

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks