Stem Cells in Drug Discovery – Technology Networks
By NEVAGiles23
Early efforts to harness the potential of stem cells for treating disease were largely focused on regeneration and the ability to repair tissues in the body through cell therapies. However, as technologies have advanced, the focus is shifting to using stem cells in drug discovery applications, such as compound screening, toxicity testing, target identification, and disease modelling. Professor Christine Mummery, from the University of Leiden tells us more and explains why stem cells are particularly suited to these applications.
Why use stem cells?
What is it that makes stem cells such an attractive option for drug discovery studies? One of the main reasons is that they make a much better model of human disease and drug reactions than animal models. As Professor Christine Mummery explains, many commonly used animal models such as mice do not accurately reflect some of the workings of cells and processes in the human body, having different immune systems and characteristics, such as heart rate, for example. This can result in problems with drugs falling down in clinical trials after showing promising results in earlier animal studies.
Using more relevant models provides not only financial savings by highlighting issues earlier in the drug discovery pipeline, but also helps efforts to reduce the number of animals used in research.
Stem cells in toxicity testing
A vital part of determining a drugs safety is assessing its cardiac toxicity. This refers to the side effects a drug can have on the functioning of the heart, such as causing arrhythmias and sudden death. As well as ensuring the safety of a drug, however, there is also a need to not unduly constrain drug development. Improvements in assay design and the implementation of the Comprehensive in Vitro Proarrhythmia Assays (CiPA) are helping to find a balance in this area.
Professor Christine Mummery tells us more about the problem of cardiotoxicity and how stem cell models and CiPA can help.
Stem cells can also play a role in testing the systemic toxicity of drugs. As Dr Glyn Stacey from NIBSC explains, pluripotent stem cell lines are increasingly being used to develop new assays that enable earlier identification of drugs that can have chronic effects on the body.
Endogenous activation of stem cells A novel and promising area of currently developing research is the ability to drive regeneration endogenously using small molecules. As Professor Angela Russell from the University of Oxford describes in the following video, we might not need to rely on using stem cells themselves, but rather small molecule therapeutics that can promote repair in damaged tissues. Circumventing the need for cells could have huge benefits for both the patient and drug developers.
What are some of the hurdles?
Stem cells certainly provide numerous opportunities to accelerate the drug discovery field, but challenges do remain.
A fundamental issue faced by all researchers in this field is ensuring the quality of the cells used. As Dr Glyn Stacey explains, a good level of quality control needs to be maintained throughout, to ensure that cells have not been contaminated or mixed up with another cell line.
Understanding signalling pathways and knowing which growth factors to add to push cells to develop into progenitor cells can also present challenges to researchers developing stem cell based screening assays. Producing sufficient numbers of relevant cell types to conduct a screen is another problem commonly faced.
The final hurdle is translation to the clinic, which relies on proving the safety of a treatment, and ensuring that it does not give rise to secondary conditions. In the case of Professor Angela Russells work, this involves taking careful steps to select compounds that act through correct pathways that wont increase the risk of cancer developing.
What does the future hold?
The roles that stem cells play in the drug discovery process are likely to continue to increase, as developments in technology enable the creation of a wider range of cells and assays. A move towards using cells with greater maturity and models that incorporate a combination of different cell types, enabling the study of interactions between cells is on the horizon. These combinations of cells will teach us a lot about drug discovery and disease, says Professor Christine Mummery.
All interviews from Stem Cells in Drug Discovery 2017 can be found here.
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Stem Cells in Drug Discovery - Technology Networks
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