Abstract

Scaffold- and Spheroid-based 3D Cell Culture Methods for Applications in Oncology and Toxicology

Joy Hu, Technical Specialist, BioTek Instruments (Taiwan), Ltd.

Over the last decade, a central focus for improving drug efficacy has been to increase the biological relevance of assays performed in the pre-clinical drug discovery process. Yet it remains difficult to simulate a drug’s in vivo response using an in vitro assay. In vitro assays typically use cells grown on two-dimensional (2D) hard plastic or glass substrates, which are not representative of the true in vivo cell environment. In tissue, cells interact with neighboring cells and with the extracellular matrix (ECM) to form a communication network that affects many cellular processes including proliferation, migration and apoptosis. In a simplified, in vitro 2D environment, most of the tissue-specific architecture, cell-cell communication and cues are lost. Therefore the need exists for advanced culture methods that better mimic cellular function within living tissue. Three-dimensional (3D) cell culture methods, in comparison, provide a matrix that encourages cells to organize into structures more indicative of the in vivo environment, thereby developing normal cell-cell and cell-ECM interactions in an in vitro environment. The most popular formats of 3D cell culture involve scaffolds built in microplate wells using a variety of materials such as hydrogels, collagen, electrospun fibers and others; and spheroids consisting of cell aggregates (~ 103 - 104 cells) that can be formed using hanging drop microplates or ultra low absorbance coated microplates. Here, we will demonstrate automated assays using both whole well detection and microscopy for applications in oncology and toxicology using both scaffold- and spheroid-based 3D cell culture methods.