Reproducibility: Changing the Policies and Culture of Cell Line Authentication

06. 2015 | Reproducibility: Changing the Policies and Culture of Cell Line Authentication  |  Read Full Article

Advances in life science research build upon the reproducibility of previously published data and findings, yet irreproducibility in basic and preclinical biological research is a pervasive, expensive and increasingly well-recognized problem. Also called replication, validation, verification or reanalysis, in simplest terms, reproducibility means that an experiment should be able to be confirmed in an independent laboratory with results that broadly support the conclusions of the original scientist.  Excluding deliberate scientific misconduct, irreproducibility typically results from errors or flaws in one or more of the following areas of the research process: reference materials, study design, laboratory protocols, and data analysis and reporting.  Irreproducible preclinical research contributes to both delays and increased costs in drug discovery.

One common contributor to irreproducibility in the life sciences is the widespread use of misidentified (including by intraspecies and interspecies cross-contamination and simple mislabeling) or microbially contaminated cell lines isolated from various human tissues. Cell lines have been used for decades to study basic biological mechanisms and serve as preclinical models for drug target discovery and to generate diagnostic hypotheses in multiple areas of biomedical research. In these uses, accurate documentation of species, sex and tissue of origin is integral to interpretation and validity of research results. It is also important to monitor genotypic or phenotypic changes (i.e., drift) that might occur over time.

Correct identification of the origin of a cell line is simple. Cell line authentication can be achieved by determining the genetic signature (by profiling or fingerprinting) and comparing it with established databases to confirm identity.  From 2011 to 2012, an international group of scientists from multiple stakeholder groups collaborated to develop an accredited standard that describes optimal cell line authentication practices based on STR (short tandem repeat) profiling.  The International Cell Line Authentication Committee was formed following publication of the STR profiling standard to make cell line misidentification more visible and to promote awareness and use of authentication testing. However, there is little evidence that authentication is widely used in the life sciences. Many researchers are simply unaware of the need to establish
and carefully maintain cell cultures and techniques, or they are aware but do nothing to validate their cell lines. Several journals, including Nature, now require or strongly recommend cell line authentication for studies they publish.  Yet, despite these efforts, new reports of misidentified or contaminated cell lines still appear in the scientific literature.

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