As is obvious to all of our readers, I suspect, the behaviour of cells in culture is greatly influenced by their shape and microenvironment. As the use of cell cultures in the development of more physiological high throughput screens increased, the need to maintain cells in a phenotypically stable state increased concomitantly. Moreover, the need to maintain the cells in a more reproducible state became of paramount importance in the quest for more relevant, high quality data from such in vivo screens. The need to reproduce more accurately a physiologically relevant state resulted (for some cell types at least) in a drive away from 2D cultures to 3D cultures, in which cell morphology can be more easily retained. Such a paradigm shift is not, however, without its problems, not least in optimization of the conditions required to maintain phenotype in cell culture, maintaining reproducibility of culture, ensuring a constant microenvironment with respect to nutrients and oxygen tension, along with a huge list of potential problems. The holy grail of obtaining cells that retain their characteristics in culture and their ability to be introduced into HTS systems, providing high quality drug screening data has been the driver for much of this research.
The free downloads available in this newsletter highlight some of the most recent developments in 3D cell culture. I will elaborate on them below.
The first article, by Amish Asthana and William S. Kisaalita of the Cellular Bioengineering Laboratory, College of Engineering, Driftmier Engineering Center, University of Georgia, Athens, GA 30602, USA, entitled “Biophysical microenvironment and 3D culture physiological relevance” discusses microenvironmental factors (MEFs) that influence cell behaviour in culture. In particular, the article deals with cell-substrate interactions and the influence of elastic moduli encountered by various gels used for cell culture. The article addresses how control of these MEFs can facilitate incorporation of such cell cultures into HTS technology with a saving in the per compound screening cost.
The second article, also by by Amish Asthana and William S. Kisaalita of the Cellular Bioengineering Laboratory, College of Engineering, Driftmier Engineering Center, University of Georgia, Athens, GA 30602, USA entitled: “Microtissue size and hypoxia in HTS with 3D cultures”, represents an earlier piece of work from the group. The article specifically deals with the effects of forces on the cells in culture and how the size of the culture can influence mechanical forces and hypoxia. The article offers practical help and guidance on rational selection of culture parameters for 3D platforms, according to specific HTS requirements.
Finally, is the review from Susan Breslin and Lorraine O’Driscoll of the School of Pharmacy and Pharmaceutical Sciences & Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland, entitled: “Three-dimensional cell culture: the missing link in drug discovery”. Continuing in a similar vein from the first two articles, Breslin and O’Driscoll discuss how cell cultures may be the GO/NO GO decision in drug development. Yet, in the past, cells may have been grown in a 2D environment, which might have major repercussions on the quality of decisions based on the data from cell culture. They comment upon the improved potential clinical relevance of decisions based upon the much more physiologically-relevant 3D culture systems and consider the relative strengths and weaknesses of 2D and 3D systems as applied to cancer drug discovery.
Steve Carney was born in Liverpool, England and studied Biochemistry at Liverpool University, obtaining a BSc.(Hons) and then read for a PhD on the Biochemistry and Pathology of Connective Tissue Diseases in Manchester University, in the Departments of Medical Biochemistry and Histopathology. On completion of his PhD he moved to the Kennedy Institute of Rheumatology, London, where he worked with Professor Helen Muir FRS and Professor Tim Hardingham, on the biochemistry of experimental Osteoarthritis. He joined Eli Lilly and Co. and held a number of positions in Biology R&D, initially in the Connective Tissue Department, but latterly in the Neuroscience Department. He left Lilly to take up his present position as Managing Editor, Drug Discovery Today, at Elsevier. Currently, he also holds an Honorary lectureship in Drug Discovery at the University of Surrey, UK. He has authored over 40 peer-reviewed articles, written several book chapters and has held a number of patents.