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Review
. 2014 May;12(4):207-18.
doi: 10.1089/adt.2014.573.

Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors

Rasheena Edmondson  1 , Jessica Jenkins Broglie, Audrey F Adcock, Liju Yang
Affiliations
Review

Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors

Rasheena Edmondson et al. Assay Drug Dev Technol. 2014 May.

Abstract

Three-dimensional (3D) cell culture systems have gained increasing interest in drug discovery and tissue engineering due to their evident advantages in providing more physiologically relevant information and more predictive data for in vivo tests. In this review, we discuss the characteristics of 3D cell culture systems in comparison to the two-dimensional (2D) monolayer culture, focusing on cell growth conditions, cell proliferation, population, and gene and protein expression profiles. The innovations and development in 3D culture systems for drug discovery over the past 5 years are also reviewed in the article, emphasizing the cellular response to different classes of anticancer drugs, focusing particularly on similarities and differences between 3D and 2D models across the field. The progression and advancement in the application of 3D cell cultures in cell-based biosensors is another focal point of this review.

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Figures

<b>Fig. 1.</b>
Fig. 1.
Schematic diagrams of the traditional two-dimensional (2D) monolayer cell culture (A) and three typical three-dimensional (3D) cell culture systems: cell spheroids/aggregates grown on matrix (B), cells embedded within matrix (C), or scaffold-free cell spheroids in suspension (D).
<b>Fig. 2.</b>
Fig. 2.
Four types of the structure of 3D spheroids based on the 3D cultures formed by a panel of 25 breast cancer cell lines. Reprinted from Kenny et al.
<b>Fig. 3.</b>
Fig. 3.
The schematic diagram of typical zones of cell proliferation in a 3D spheroid, with the models of oxygenation, nutrition, and CO2 removal. Reprinted from Lin and Chang.
<b>Fig. 4.</b>
Fig. 4.
Cell survival obtained by fluorescent microculture cytotoxicity assay (FMCA), upon the treatment of four standard anticancer drugs to HCT-116 cells in 2D monolayer and 3 day and 6 day old 3D spheroids. Reprinted from Karlsson et al.
<b>Fig. 5.</b>
Fig. 5.
(A) Schematic diagram of an electrochemical biosensor with 3D cell culture in degradable matrix on a flat electrode. Reprinted from Lin et al. (B) The comparison of the principle and the typical signals of the electrochemical biosensors with 2D and 3D cell cultures. Reprinted from Jeong et al. (C) A cavity-based electric impedance biosensor for 3D cell spheroids. Reprinted from Kloss et al. (D) A capillary-based electric impedance biosensor for 3D cell spheroids. Reprinted from Hildebrandt et al.
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