Drug Discovery


Figure 3


Characteristics of primary cells versus immortalised cell lines


this can have costly implications for pharmaceutical companies. In fact, 18-36% of cell lines used in published


research are misidentified or cross-contaminated8. Furthermore, the results of assays using cell lines cannot easily be replicated in vivo due to cell line variability and disparity from the in vivo environ- ment. The use of uncharacterised cell lines has become such an issue that the NIH requires cell line authentication in funded publications. Unlike continuous cell lines, human primary


cells provide researchers with an in vitro model closest to the tissue type that they are isolated from. Primary cells have limited lifespan but also have a low mutation rate, resulting in less variation from the original tissue. When studying cancer progression or cancer development in vitro, it is typically recommended that such studies be con- ducted within normal primary cells, which then can be exposed to cancer biomarkers. More impor- tantly, when studying primary cells, researchers are also acquiring an added opportunity to study donors. Several factors such as age, medical histo- ry, race and sex can be considered when building a comprehensive profile of drug substrates within these in vitro models. When evaluated in comparison studies, cell lines


and primary cells have demonstrated differences in behaviour and dose responses. With a growing trend towards personalised medicine and a clear need to improve reagents used across preclinical research, primary cells offer a natural and more robust solution for target discovery and validation. Such donor variability and tissue complexity can- not be achieved as easily with cell lines that are very systematic and uniform in nature. In order to standardise cancer data against a


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normal state, the most sensible factor to incorpo- rate would be ‘normal’ primary human cells as an optimal control. This allows researchers to under- stand the progression from a normal tissue-like state to a cancerous one. More importantly, it allows taking the donor characteristics into consid- eration and, as such, a comprehensive cancer pro- file is built. As a result, pharmaceutical companies and research laboratories are now seeing the value of using ‘normal’ human primary cells as necessary side-by-side controls to establish a more accurate baseline for cancer development. Such studies have traditionally been performed on immortalised cell lines which provide the uniformity in an experi- ment but do not capture the true diversity of a liv- ing tissue. As more and more researchers incorpo- rate ‘normal’ primary cells as side-by-side controls in cancer experiments, basic research and drug dis- covery can move closer to generating better data and better outcomes.


Primary cells – what’s next? Successful targets progress through the initial phas- es of drug discovery to assay development, where a need for higher throughput approaches calls for new technologies, such as 3D cell culture models. These specialised models can better mimic the nat- ural cellular in vivo environment, resulting in a more biologically relevant approach and providing more reliable data. A clear need has emerged recently within the pharmaceutical drug discovery pipeline for 3D culture technologies that can pro- vide throughput in a 96-well, 384-well and 1536- well format, allowing researchers to generate large numbers of tissue-like models for drug screening. A combination of using human primary cells in 3D culture models is currently considered the gold


Drug Discovery World Spring 2018


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