Systems Biology Approaches Supported by Microdevice Engineering

Elmar Heinzle and Fozia Noor, Saarland University, Germany

Systems Biology is presently developing with a breathtaking pace, particularly “omics”-type analytical methods allowing the analysis of virtually all molecules of living cells as DNA, RNA, proteins and metabolites. Bioinformatic and other computational methods permit increasingly describing cellular metabolism in computer models. Using such holistic methods promises improved predictivity of cellular events as response to genetic or environmental changes. Therefore systems biology approaches are particularly promising new opportunities for toxicity prediction based on a limited number of experiments. For highest relevance experiments should be carried out in cellular systems as close as possible to the human in vivo situation. Eventually prediction should be possible for all relevant human tissue and for the body as a whole. Presently, one of the most significant bottlenecks is the lack of relevant, robust and reproducible cellular systems. Cell lines available now are usually derived from cancer patients. Since the establishment of stem cell technologies there is a big hope that relevant differentiated cells will soon be derived reproducibly from stem cells. Since virtually all human cells exist in tissues contacting multiple other cells of the same or different types, it seems most relevant to use such organotypic cultures for toxicity experiments. In recent years a whole series of 3D culture techniques and devices were described in the literature, some of them involving micro- or even nano-structures to support tissue formation. Systems useful for liver cell culture will be reviewed and selected experimental results will be presented using primary human cells as well as liver cell lines. It will also be outlined how data of such systems might be used for creating data relevant for later toxicity prediction using systems biology methods.