A new survey of almost 450 biomedical researchers from every major stakeholder group (e.g., academia, industry) conducted by the Global Biological Standards Institute (GBSI) shows little has changed in cell line authentication and culture practices in the past decade -- practices that contribute to irreproducible research, and delays and increased costs of drug discovery. The results are detailed in "The culture of cell culture practices and authentication -- Results from a 2015 Survey," by Leonard P. Freedman, Ph.D., lead author, published today in the open access journal BioTechniques.
"Cell line authentication is essential to producing high quality of biomedical research and ultimately to the discovery of treatments and cures," said Freedman, who is president of GBSI. "Our survey reveals that the majority of biomedical researchers still do not authenticate their cells. And while support for change is strengthening, the scientific community has still not embraced cell authentication as an expected part of the research process."
Cell lines are cultured, passaged and processed today using widely varying quality control procedures, but sharing cell lines remains endemic. Consequently, misidentified cells -- including inter- and intraspecies cross-contamination as well as simple cell line naming and mislabeling errors -- continue to plague the scientific literature.
The financial implications of misidentified or contaminated cell lines can be profound. A search of the National Institutes of Health RePORTER database revealed 9,000 projects and sub-projects using cell lines at a total estimated expenditure of $3.7 billion dollars. Using a conservative estimate of 20 percent use of misidentified or contaminated cell lines would equate to more than $700 million dollars annually in research that could be at risk in the United States alone.
The online survey was conducted between April 16 and June 5, 2015, and included members of more than 20 prominent biomedical research societies and organizations. Of 446 total respondents, 73 percent rated themselves as either expert or above average cell-culturists.
More than half of respondents -- 52 percent -- "never" perform authentication or other species-related quality control tests on the cell lines used in their experiments. Moreover, 74 percent never conduct STR (short-tandem repeat) DNA profiling, the accepted standard for authentication. Although respondents were more likely to perform some sterility-related (microbial contamination) quality controls, particularly visual inspections, such inspections will not typically detect mycoplasma bacteria-infected cells.
The top three respondent-identified barriers to performing cell line authentication were cost (61 percent), time (53 percent), and delays in research (35 percent). More troubling is the apparent complacency surrounding the need to authenticate cell lines: 24 percent reported "I don't see the necessity; I am careful"; 22 percent reported that their laboratory manager or principal investigator is "unaware of or ignores the issue."
While a percentage of researchers hold to old patterns, respondents overwhelmingly agreed that not performing cell line authentication could adversely impact research quality. Almost 75 percent support development and use of additional standardized techniques and procedures for authenticating cell lines, such as single-nucleotide polymorphism (SNP) genotyping. They also support expanded training, funding, and cell culture best practices.
Only 62 percent of respondents received specific training on the problems associated with cell line misidentification (cross-contamination) and mislabeling, and less than one-third were trained on the importance of cell line authentication as a quality control measure. Further, only 65 percent of respondents indicated that their laboratory follows specific written procedures for the handling and storage of cultured cells and cell lines.
"The failure to authenticate cell lines is still not an impediment to publication or to obtaining research funding," said Freedman. "A systematic approach by the entire biomedical research community that ensures routinely documented cell authentication is needed to resolve this global problem. In its absence, the accuracy of published research using cell lines is in question." "Furthermore, the scientific community must commit sufficient time, resources, and expertise to adequately train and educate young and experienced scientists alike in best practices for cell culture experiments. While advancing technology continues to diminish the cost and time constraints cited by most respondents, training researchers is key to making cell authentication routine."
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