Have your say! Cell culture in 3D – Exploring the potential for drug discovery
Cellectricon has supported this shift in drug discovery screening from high throughput to high content, by providing state-of-the-art cellular screening technologies and services. With the advent of 3D culturing technologies, it is thought that 3D culture will become essential for increasing assay relevance. However, many questions still remain to be answered as to the relevance of 3D cell cultures for drug discovery. In an effort to gain more insight into the particular constraints, difficulties and possibilities that are faced by researchers working with 3D cultures, we have created an industry survey.
We encourage any scientist to enter this quick survey, all thoughts and insights are valued, whether you have experience of working with 3D cultures or not. By entering the survey, you will help to shape the ongoing development of our products and services, and all participants will also be entered into our prize draw for a $150 amazon.com voucher and will also receive a copy of the findings.
Neuronal networks in 3D
Neuronal communication in vivo involves complex and dynamic three-dimensional (3D) networks. Conventional neuronal cell culture however, entails a planar two-dimensional (2D) cell environment that results in uncharacteristic cell-cell contacts and network formation . Most likely, in vitro culture of any type of cell in 2D overlooks parameters that are important for the reproduction of normal cell and tissue physiology. Therefore, the scientific community has become increasingly aware that primary cells may need to be cultured in 3D in order to attain physiologically relevant cell properties, including typical cell-cell communication and, for neurons, network plasticity.
Typically, 3D cultures are achieved by the use of various types of scaffold materials that provide a culture environment that takes into account the spatial organization of the cell . The aim of the scaffold is to substitute the normal extracellular matrix of the tissue of interest in order to reproduce native cell function, and two main types of materials are typically used in the production of cell culture scaffolds:
- Natural polymers – such as collagen, fibrin and alginate, which can be extracted from animals or human tissue. Such materials generally exhibit good biocompatibility and low toxicity, but variability between batches and difficult processing are drawbacks for some of the polymers .
- Synthetic polymers – are easier to process compared to natural polymers, giving rise to more predictable results .
Neuronal cell culture, which is currently one of our main focuses, requires the development of suitable methods for 3D culture. Interestingly, a novel electrospun polyurethane nanofiber-based 3D cell culture system was recently developed, in which central nervous system neurons were able to grow in three dimensions. The neurons were even able to form complex network structures that had not previously been observed in vitro . Soft tissues, such as neural tissue, are sensitive to the mechanical substrate , and therefore, scaffolds with mechanical properties that support neurite extension are important.
Optimizing 3D cell cultures for drug discovery
So how does one select technology for the best possible results and combine this with the efficacy and ease of automation? Also, is it possible to meet the requirement of consistency across the assay when utilizing animal-derived components in the 3D culture? At Cellectricon, we believe that future exploration of 3D cultures for drug discovery should not only consider 3D biology and cell culture, but also the impact of price and scalability – as well as integration into modern automated cell-based screening systems.
Your thoughts and experiences from 3D cell culturing would be greatly appreciated – so please take our survey.
Charlotta Blom, Senior Scientist at Cellectricon
Charlotta is a part of the Cellectricon Discovery Services team and her main responsibility is to identify and drive implementation of phenotypic disease-relevant synaptic transmission assays. Charlotta previously held a postdoctoral research position at the Sahlgrenska Academy, Gothenburg University, where she studied mechanisms involved in stem cell migration and stroke repair. Prior to this, she was a Postdoctoral Fellow at the Queensland Brain Institute, University of Queensland, Australia, where she studied molecular mechanisms of brain development. Charlotta earned her PhD in 2005 at Lund University, Sweden, with a thesis on peripheral nerve regeneration.
 Puschmann TB, de Pablo Y, Zanden C, Liu J, Pekny M. A Novel Method for Three-Dimensional Culture of Central Nervous System Neurons. Tissue engineering Part C, Methods 2014.
 Haycock J. 3D Cell Culture: A Review of Current Approaches and Techniques. In: Haycock JW editor. 3D Cell Culture: Humana Press; 2011. pp. 1-15.
 Balgude AP, Yu X, Szymanski A, Bellamkonda RV. Agarose gel stiffness determines rate of DRG neurite extension in 3D cultures. Biomaterials 2001; 22: 1077-1084.