Drug Discovery
Enabling the promise of STEM CELLS
The remarkable potential of stem cells to generate several hundred differentiated cell types is driving their use for regenerative medicine and for supporting the traditional drug discovery and development process (Figure 1). However, sustained progress in these areas is dependent on advances in the ability to: grow these cells; direct, and control their differentiation; and produce the quantities needed for clinical trials and therapies in a cGMP (current Good Manufacturing Practices) environment. This article will examine advances taking place on both the lab bench and the pharmaceutical production floor that are helping to bring the promise of stem cells closer to reality.
E
very cell type has its own unique needs when grown in vitro and stem cells are no exception. Stem cells, and in particular human embryonic stem (ES) cells, have earned a reputation for being labour intensive and difficult to grow and control in culture. A number of fac- tors contribute to the labour-intensive upkeep of stem cell cultures: the cells must typically be fed daily; manual rather than enzyme-based passaging is often required; and differentiated colonies may require separation from undifferentiated colonies under a dissection microscope, which can be quite tedious. In addition, this excessive handling can increase the risk of contamination.
Further complicating matters, human ES cells are typically co-cultured with feeder layers of mouse fibroblast cells. Use of feeder layers requires two cell types to be maintained in parallel and introduces mouse proteins into the culture system. Alternatively, stem cell cultures can be grown on extracellular matrix extracts and supplement- ed with conditioned medium from mouse fibrob- last cultures. Although this approach eliminates the need for feeder layers, the system still contains undefined animal proteins, as well as possible contaminants. Inclusion of fetal bovine serum in stem cell media further contributes to an ill-
Drug Discovery World Spring 2011
defined culture system. The use of mouse feeder layers and animal serum are particularly prob- lematic in the culturing of stem cells for possible therapeutic applications.
While significant progress has been made towards more defined culture conditions, develop- ment of animal-free culture systems has lagged. Use of serum replacements has removed some vari- ability associated with fetal bovine serum and has led to human ES cell media that is ‘serum-free’. However, serum replacements still may contain bovine serum albumin.
By Robert Shaw and Dr Jeff Till
Figure 1: Application of stem cells for both therapeutic and drug discovery applications 15
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