The medical and academic research communities have been holding their collective breath for the past 10 years in anticipation of the breakthrough cures for such devastating diseases as Alzheimer’s and diabetes as well as the seemingly miraculous recovery of those suffering from traumatic spinal cord injury; all this because of the great promise of stem cells therapy.
We in the research community it seems have realised that, although the promise and potential still exists, we still have volumes to learn about the nature of stem cells and perhaps years of hard work ahead of us before many of those breakthrough actually become available for therapeutic use. In the meantime, the interest in stem cells has widened beyond the more published therapeutic applications. It seems human stem cells, embryonic and adult, are very much in the forefront as tools for drug discovery, efficacy and toxicology1,2.
Utilising stem cells for these applications certainly bridges the animal to human gap, the in vitro to in vivo gap and very likely means those compounds that reach phaseI clinical trials are much more likely to proceed on to commercialisation. It may also be safe to assume, if applied at the early stages of drug candidate development that unsuitable compounds that might otherwise continue along the pipeline to clinical trials would be identified thus saving time, resources, money, as well as risk to patients.
In general, stem cells are differentiated to a specific target cell such as cardiomyocytes1 or neurons2. The use of stem cells offers a renewable and theoretically inexhaustible source of cells.
Given sufficient markers for characterisation of the specific cell type of interest, this method then yields a homogeneous cell population of sufficient density to conduct genomic, epigenomic, developmental, functional, and other cell-based assays that will in total determine the safety and efficacy of a given compound.
Adult and embryonic stem cells from various animal models have also been tested in this manner. While it appears the use of animal model-derived cells certainly contribute valuable data, human cells would tend to yield the most valuable and directly relevant information3.
The use of stem cells to generate somatic or post-mitotic cells, which are most susceptible as drug targets – eg, hepatic, cardiac, and neural – will most certainly ensure a more robust and reliable system for critical pharmacological testing such as target validation and structure-activity relationship3.
Robust and stable cultures are by far the most critical factor in these cell-based assays. Cultures must contain a very high proportion of cells that demonstrate the appropriate markers and/or phenotype in order to collect valid, relevant data. To this end Sigma has developed Stemline platform of proprietary stem cell media.
- Stemline Hematopoietic Stem Cell Expansion Medium.
- Stemline Mesenchymal Stem Cell Expansion Medium.
- Stemline Neural Stem Cell Expansion Medium.
With the exception of our mesenchymal medium, these formulations are serum-free. All of our Stemline formulations demonstrate exceptional cell stability and marker expression. Each has been formulated to support high density populations with expansion rates for each targeted cell type are robust with peak density in 7 to
14 days. Cultures also yield high viable populations in addition to the ability to maintain high percentages of targeted phenotypes and morphologies.
While expansion media are critical, the quality and activity of the cytokines to differentiate stem cells also plays a large part in the success of efficiently and accurately driving populations toward a specific fate, such as taking mesenchymal cells to cardiomyocytes or neurons.
Sigma also provides a very broad range of native and recombinant source growth factors and cytokines for use in cell growth and differentiation as well a complete selection of antibodies suitable for cell characterisation.
Given the current advantages and intense interest in using stem cells as screening tools in drug discovery we anticipate brisk evolution in the area.
Lisa Masterson is Product Manager – Regenerative Medicine, Sigma-Aldrich Corp, St Louis, MO, USA. www.sigmaaldrich.com
References:
- Chaudrhary, KW, et al, Toxicol. Sci, 90(1):149-58, March 2006;
- Pouton, Colin W. and John M. Haynes, Nature Reviews Drug Discovery 6, 605 - 16, August 2007;
- Cezar, GC, Curr. Opin. Chem. Biol., 11(4):405-9, A ugust 2007.
