DiscussionOne of the biggest pressures for innovation is necessity, and this is nowhere truer than in the pharmaceutical industry which has come under increasing pressure to overhaul the drug discovery and development process. The challenge is to fix the high rate of attrition, whereby too many promising drug candidates fail at late stages in the process. Although assays developed using static cell culture techniques can provide valuable insights, the limitations of these systems in only partially replicating normal biological processes impacts on the utility and reliability of the resultant data.
Advances in the area of in vitro testing offer one of the most promising solutions to tackle this huge attrition problem. In vitro models have become more sophisticated and are now at a stage where they can provide an effective alternative to some in vivo experiments Creating an in vitro environment which encourages cells to behave in the way they do in their natural situation allows for the development of more predictive models as well as providing the framework to capture more of the complexities of normal biological function and even replicate inter-individual variability. Cells experience nutrient gradients, pressure and flow, and they communicate with each other. Cells cultured in static media in well plates, whether primary cells or cell lines, cannot replicate this highly organised structure. Quasi-Vivo® perfusion systems – which provide nutrient flow and allow for co-culture and the development of 3D structures – are being used to culture cells with improved viability and function. Cells cultured in this environment have been shown to retain phenotype and exhibit long-term metabolic competency. This increases the prospect of obtaining more meaningful data from in vitro assays. Some preliminary results are presented that illustrate the potential for advanced in vitro cell culture, including the use of live cell imaging in the QV900. The Quasi-Vivo® perfusion systems provide a stepping stone towards the more speculative organ-on-a-chip or human-on-a-chip technology.
A key part of the strategy to gradually replace animal testing is to find some common types of experiment that can be done better in vitro than in vivo, and that doing so will result in both scientific and ethical gains. This paper will include 'case studies' that illustrate the ways in which culture models can be used to answer a range of important biological questions of direct relevance to human development, physiology, disease and healing.