Alginate-Based Three-Dimensional In Vitro Tumor Models: A Better Alternative to Current Two-Dimensional Cell Culture Models

Abstract

The conventional two-dimensional (2D) cell culture models, although providing considerable information about the cellular dynamics, often fail in vivo. In the area of oncology drug discovery and development process, the tumor microenvironment poses a significant challenge owing to the complexity of tumor stroma, and the traditional 2D in vitro systems fail to mimic the extracellular matrix (EC) and cell-to-cell interaction-based modulations. Three-dimensional (3D) cell culture systems/matrices, also designated as scaffolds, offer an excellent platform to study the tumor microenvironment in a more realistic way. Alginate matrices are widely used for cellular encapsulation, cell transplantation, and tissue engineering. Alginate-based 3D gels and scaffolds have emerged as a prime matrix to simulate tumor microenvironment closer to physiological condition. Alginate being hydrophilic provides uniform matrix for growth and proliferation. The alginate scaffolds and hydrogels have been used to investigate the cytotoxicity, apoptosis, and penetration of conventional drugs as well as various formulations into the in vitro tumor scaffolds/spheroids. Another advantage of alginate-based matrices for 3D cultures is that the cancer stem cell (CSC) niches can be better understood owing to the inherent 3D nature of CSCs. Moreover, the use of 3D systems gives a better impression of the physiological architecture; unique cellular interactions can occur and improve the functional properties. In this chapter, initially we compare and contrast 2D and 3D cell culture systems and the pitfalls of the conventional in vitro tumor models. Then a brief introduction of alginate-based 3D scaffolds is provided. Various in vitro models based on alginate scaffolds (AlgiMatrix™) and hydrogels are briefed with the parameters studied and the associated advantages. Future improvements in the 3D cell culture based on alginate matrices are thought through, and the possible future directions are provided. In conclusion, results from different studies give an indication that high-throughput in vitro 3D tumor models based on alginate can be prepared to study the effect of various anticancer agents and various molecular pathways affected by the anticancer drugs and formulations.