Three-dimensional cell culture systems as an in vitro platform for cancer and stem cell modeling

Abstract

Three-dimensional (3D) culture systems are becoming increasingly popular due to their ability to mimic tissue-like structures more effectively than the monolayer cultures. In cancer and stem cell research, the natural cell characteristics and architectures are closely mimicked by the 3D cell models. Thus, the 3D cell cultures are promising and suitable systems for various proposes, ranging from disease modeling to drug target identification as well as potential therapeutic substances that may transform our lives. This review provides a comprehensive compendium of recent advancements in culturing cells, in particular cancer and stem cells, using 3D culture techniques. The major approaches highlighted here include cell spheroids, hydrogel embedding, bioreactors, scaffolds, and bioprinting. In addition, the progress of employing 3D cell culture systems as a platform for cancer and stem cell research was addressed, and the prominent studies of 3D cell culture systems were discussed.

Keywords: Cancer; Disease modeling; In vitro screening platform; Stem cells; Three-dimensional cultures.

Figure 1

Schematic diagrams of the traditional two-dimensional monolayer cell culture and three-dimensional cell culture systems. A: Traditional two-dimensional monolayer cell culture; B: Three-dimensional cell culture systems; C: The structure of three-dimensional spheroid with different zones of cells with the models of oxygenation, nutrition, and CO₂ removal. Three-dimensional spheroid from inside to outside. The regions are necrotic zone (innermost), quiescent viable cell zone (middle), and proliferating zone (outermost).

Figure 2

Different techniques used for three-dimensional cell cultures. These techniques include: A: Liquid overlay; B: Hanging drop; C: Hydrogel embedding; D: Spinner flask bioreactor; E: Scaffold; F: Three-dimensional bioprinting.

Figure 3

Potential applications of three-dimensional cell culture systems. The invention of three-dimensional cell culture systems could be applied into various aspects, for instance anticancer drug screening, tissue engineering, cancer biology, and clinical uses.