The need for new tools and technologies to decrease the cost of drug discovery and reduce animal testing has been long discussed. Recently, the director of the Center for Drug Evaluation and Research at the FDA called for “new evaluative tools for predicting, understanding, and assessing the effects of [drugs] in the relevant species (people).” Such tools have potential for reducing costly late-stage failures by providing an in vivo-like early-stage evaluation of efficacy and toxicity.
Three-dimensional (3D) cell cultures, in formats such as spheroids, gels, scaffolds, and bioreactors, have great potential as predictive tools in drug discovery. 3D cell cultures possess many features that mimic the in vivo microenvironment, which are lacking in traditional two-dimensional (2D) cell cultures such as physiological cell-cell and cell-extracellular matrix (ECM) interactions and mass-transfer gradients.
With the implementation of 3D cell cultures into the drug screening process, more physiological data can be obtained long before animal testing. Companies can then make better-informed decisions about which compounds are most promising, lowering the cost and time to get a drug to market.
Cellular spheroids, self-assembled microscale 3D aggregates of cells, have significant potential as models for drug screening. They are reproducible, versatile, and well-characterized. Spheroids possess physiological cell-cell contacts, secrete their own ECM, have nutrient, drug, and oxygen mass transfer gradients, and are often used as 3D models of many types of avascular tissues, tumors, and embryoid bodies.
3D Biomatrix Perfecta3D® Hanging Drop Plates facilitate easy and consistent spheroid formation in a 96- or 384-well format. Users pipet a cell suspension into each well, and, due to the well geometry, the suspension hangs below it (Figure 1). Since there is no surface to attach to, the cells aggregate and form a spheroid in the well.
The hanging drop confines spheroid formation to one per well, allowing the user to control the spheroid diameter with the type and number of cells in each well. Spheroids composed of 50–15,000 cells have been formed in Perfecta3D Hanging Drop Plates. Access holes allow for media exchange and the addition of compounds, reagents, or additional cells.
This article presents data on utilizing spheroid cultures to evaluate anticancer drugs and to build tissue and tumor co-culture models. This data demonstrates the potential of spheroid cultures as a predictive drug discovery tool.