Three-Dimensional Tissue Models for Drug Discovery and Toxicology

Francesco      Pampaloni; Ernst   H. K.   Stelzer; Andrea      Masotti

Abstract

Launching a new drug on the market is an extremely time-consuming and expensive process. The total costs from the lab bench to the patients bedside are in the range of $800 million for each new compound. Innovative preclinical assays are urgently needed to select the most promising drug candidates. High-throughput molecular screening does not provide information on the effects on cellular functions. Testing on animals is expensive, ethically controversial, and poorly predictive of the response in humans. Conventional two-dimensional (2D) cellular assays do not accurately reflect the drug response in vivo. To overcome these limitations, biotechnologists are developing three-dimensional (3D) cultures. 3D cultures provide more accurate compound screening and can eliminate toxic and ineffective substances at an early stage. Moreover, 3D cultures can accomplish the 3R agenda (refinement, reduction, and replacement) for the replacement of toxicity testing on animals. We provide an up-to-date overview on the patents in the field.

Keywords: 3D cell culture, extracellular matrix, ECM, cellular spheroid, microcarrier culture, microfluidic culture, organotypic culture, drug discovery, toxicity screening, 3R agenda