In recent years, there has been a significant decline in the success rate of drug candidates in clinical trials. This situation has put pharmaceutical companies under immense pressure to reduce expenses and increase productivity. As a result, drug researchers have stepped up their use of high-content screening of large chemical libraries. Larger screens, however, do not always produce more leads.
Use of target cells in culture that more closely resembles the target organ in vivo can increase predictability. In addition, the increased biological relevance of cell lines and their drug targets decreases late attrition in trials.
At the same time, an increase in the use of cell-based therapeutic strategies has escalated the need for cells that are of consistent quality and in sufficient quantities. Automated platforms are being used to meet the increased demand for in vivo mimetic organotypic cells. The ability to grow large numbers of cells in a consistent and reliable fashion is directly related to the automation of the cell culture process, sample handling, imaging, and assaying.
Over the last 30 years, the drug screening industry has seen a trend toward using more biologically relevant 3-D surfaces for cell-based screening. Cells interact with neighboring cells and the extracellular matrix (ECM) in vivo by means of biochemical and mechanical cues. Cell cultures that replicate real tissue interactions are better candidates for proliferation, migration, apoptosis, and tumorigenesis models.
Currently, the vast majority of cell culture for cell-based data harvesting occurs in flat, hard, plastic dishes. It is widely accepted that this system has limitations in biological relevance, thus, a number of new scaffolds have been developed to mimic the ECM in vivo environment. Recent research has demonstrated that coating flat plasticware with reconstituted basement membrane (rBM) provides additional insights into the extracellular context in tumorigenesis and reveals differences in receptor activity in human breast cancer cells. Though such scaffolds have revealed much about cell behavior, microcarriers take 3-D biology to the next level.