|
Sign In to gain access to subscriptions and/or personal tools.
|
The Use of 3-D Cultures for High-Throughput Screening: The Multicellular Spheroid Model
Leoni A. Kunz-Schughart
Institute of Pathology, University of Regensburg, 93042 Regensburg, Germany
James P. Freyer
Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM, USA
Ferdinand Hofstaedter
Institute of Pathology, University of Regensburg, 93042 Regensburg, Germany
Reinhard Ebner
Avalon Pharmaceuticals Inc., Germantown, MD, USA
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.
Key Words: cell-based assay • 3-D culture • spheroid • co-culture • anti-tumor drug testing
Journal of Biomolecular Screening, Vol. 9, No. 4,
273-285 (2004)
DOI: 10.1177/1087057104265040
 CiteULike  Complore  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter What's this?
This article has been cited by other articles:
|
|
|
|
 
F. Hirschhaeuser, T. Leidig, B. Rodday, C. Lindemann, and W. Mueller-Klieser
Test System for Trifunctional Antibodies in 3D MCTS Culture
J Biomol Screen,
September 1, 2009;
14(8):
980 - 990.
[Abstract]
[PDF]
|
|
|
|
|
|
|
V. S. Nirmalanandhan and G. S. Sittampalam
Stem Cells in Drug Discovery, Tissue Engineering, and Regenerative Medicine: Emerging Opportunities and Challenges
J Biomol Screen,
August 1, 2009;
14(7):
755 - 768.
[Abstract]
[PDF]
|
|
|
|
|
|
|
C. A. Powell
Rounding Up Apoptosis Resistance Targets in Lung Cancer
Am. J. Respir. Cell Mol. Biol.,
July 1, 2009;
41(1):
7 - 8.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S.-Y. Sung, C.-L. Hsieh, A. Law, H. E. Zhau, S. Pathak, A. S. Multani, S. Lim, I. M. Coleman, L.-C. Wu, W. D. Figg, et al.
Coevolution of Prostate Cancer and Bone Stroma in Three-Dimensional Coculture: Implications for Cancer Growth and Metastasis
Cancer Res.,
December 1, 2008;
68(23):
9996 - 10003.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. M. Wilson, D. Barbone, T.-M. Yang, D. M. Jablons, R. Bueno, D. J. Sugarbaker, S. L. Nishimura, G. J. Gordon, and V. C. Broaddus
mTOR Mediates Survival Signals in Malignant Mesothelioma Grown as Tumor Fragment Spheroids
Am. J. Respir. Cell Mol. Biol.,
November 1, 2008;
39(5):
576 - 583.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Friedrich, W. Eder, J. Castaneda, M. Doss, E. Huber, R. Ebner, and L. A. Kunz-Schughart
A Reliable Tool to Determine Cell Viability in Complex 3-D Culture: The Acid Phosphatase Assay
J Biomol Screen,
October 1, 2007;
12(7):
925 - 937.
[Abstract]
[PDF]
|
|
|
|
|
|
|
Y. Ibold, S. Frauenschuh, C. Kaps, M. Sittinger, J. Ringe, and P. M. Goetz
Development of a High-Throughput Screening Assay Based on the 3-Dimensional Pannus Model for Rheumatoid Arthritis
J Biomol Screen,
October 1, 2007;
12(7):
956 - 965.
[Abstract]
[PDF]
|
|
|
|
|
|
|
A. Ivascu and M. Kubbies
Rapid Generation of Single-Tumor Spheroids for High-Throughput Cell Function and Toxicity Analysis
J Biomol Screen,
December 1, 2006;
11(8):
922 - 932.
[Abstract]
[PDF]
|
|
|
|
|
|
|
L. A. Kunz-Schughart, J. A. Schroeder, M. Wondrak, F. van Rey, K. Lehle, F. Hofstaedter, and D. N. Wheatley
Potential of fibroblasts to regulate the formation of three-dimensional vessel-like structures from endothelial cells in vitro
Am J Physiol Cell Physiol,
May 1, 2006;
290(5):
C1385 - C1398.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Bartholoma, E. Gorjup, D. Monz, A. Reininger-Mack, H. Thielecke, and A. Robitzki
Three-Dimensional In Vitro Reaggregates of Embryonic Cardiomyocytes: A Potential Model System for Monitoring Effects of Bioactive Agents
J Biomol Screen,
December 1, 2005;
10(8):
814 - 822.
[Abstract]
[PDF]
|
|
|
|
|
|
|
P. Bartholoma, Impidjati, A. Reininger-Mack, Z. Zhang, H. Thielecke, and A. Robitzki
A More Aggressive Breast Cancer Spheroid Model Coupled to an Electronic Capillary Sensor System for a High-Content Screening of Cytotoxic Agents in Cancer Therapy: 3-Dimensional In Vitro Tumor Spheroids as a Screening Model
J Biomol Screen,
October 1, 2005;
10(7):
705 - 714.
[Abstract]
[PDF]
|
|
|
|
|
