Failure to monitor cell lines for cross-contamination or misidentification, a problem that has persisted for cancer cell lines for decades, may result in compromised data and ultimately irreproducible results. Many journals and now funding agencies, including the National Institutes of Health (NIH) have guidelines set in place for the authentication of cell lines used in research studies.
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Cell Line Authentication Testing
NIH Guidelines for Funding
In June 2015, the NIH released Notice Number: NOT-OD-15-103 "Enhancing Reproducibility through Rigor and Transparency" to notify researchers of the revised application instructions for funding of grants submitted starting January 25, 2016.
"All research builds upon prior research, which may include observations, preliminary data, or published literature. ...NIH has always strived to fund projects that are based on a strong foundation."
The notice goes on to state, "NIH expects that key biological and/or chemical resources will be regularly authenticated to ensure their identity and validity for use in the proposed studies." The key biological resources list includes cell lines.
For More information:
Authentication of Key Biological and/or Chemical Resources in NIH Grant Applications - by Dr. Michael Lauer, NIH Deputy Director for Extramural Research
Which journals have guidelines for cell line authentication prior to publication*?
*For a full description of guidelines, see instructions to authors for all journals
American Association for Cancer Research (AACR) Publications
Excerpt from Guidelines: "If cell lines were used in the research, a statement addressing the following points must be included in the Materials and Methods section of the manuscript:
Bentham Science Publications
Excerpt from Guidelines: "Authors are therefore required to provide authentication of the origin and identity of the cells by performing cell profiling..."
BioMed Central Journals - includes but is not limited to:
Excerpt from Guidelines: “If human cell lines are used, authors are strongly encouraged to include the following information in their manuscript:
Excerpt from Guidelines: "Authors are encouraged to authenticate all cell lines used in their research efforts. BioTechniques specifically requires authors to check any cell lines used in their experiments against the current database of misidentified cell lines curated by the International Cell Line Authentication Committee (ICLAC)..."
Cancer (Journal of the American Cancer Society)
Excerpt from Guidelines: "Manuscripts based on research using cell lines must include a statement addressing the following points in the Methods section of the manuscript:
Excerpt from Guidelines: "Carcinogenesis requires authors to report on the authentication of all cell lines reported in their research."
Cell Biochemistry and Biophysics
Excerpt from Guidelines: "Authentication of Cell Lines - Verification of the identity of cell lines must be included in Materials and Methods section of Research manuscripts and the methodology employed referenced in the Bibliography."
Cell Biology International
Excerpt from Guidelines: “Authors must ensure that any cell lines used (1) are certified as being the designated type, (2) have been checked to ensure they are free of contamination, and (3) have been used from young stock..."
Clinical Orthopaedics and Related Research
Excerpt from Guidelines: “Authors are encouraged to take a two-step approach to the problem. First, use existing resources to identify contaminated cell lines. ...Second, the cell line must be proven authentic, even if cross contamination has not been reported."
Endocrine Society Publications
Excerpt from Guidelines: "Endocrine Society editorial policy will require that all cell lines used and described in submitted manuscripts be authenticated."
In Vitro Cellular & Developmental Biology - Animal
Excerpt from Guidelines: "Authors must state:
International Journal of Cancer
Excerpt from Guidelines: "...studies dealing with established human (tumor) cell lines must provide authentication of the origin and identity of the cells. This is best achieved by DNA (STR) profiling..."
Investigative Ophthalmology and Visual Science (IOVS)
Excerpt from Guidelines:"In light of recent events, we strongly suggest that STR analysis be used to validate the authenticity of cell lines used in papers submitted to IOVS."
Journal of Hepatology
Excerpt from Guidelines: "In the ‘Materials and methods’ section, the source of cells utilized (catalog number if obtained from vendor or cell bank, species, sex, strain, race, age of donor, whether primary or established) should be clearly indicated. The methods section should state if cell line authentication has been carried out and by what method (e.g., STR profiling) and when authentication testing was last performed for that cell line. Authors should be able to provide the test results upon request. Mycoplasma contamination testing status must also be reported."
Journal of Molecular Biology
Excerpt from Guidelines: “In keeping with NIH guidelines, the Journal considers it to be good practice for cultured cell lines to be authenticated. A description of the methods used to authenticate cells should be included in the Materials and Methods section. Authors are expected to check that cell lines used in their experiments are free from mycoplasma infections.”
Journal of the National Cancer Institute
Excerpt from Guidelines:"Authors of provisionally accepted manuscripts that use cell lines should state the methods used to authenticate any cell lines used in their studies and should give the date of the last authentication."
Excerpt from Guidelines:"Manuscripts reporting experiments in which immortalized cell lines are used must include data and documentation that demonstrate that the actual cells used in the experiments reported in the manuscript exhibit the correct phenotype and genotype. Authors are must read the article written by the editors on the authentication of cell lines (The Editors. On authentication of cell lines. Mol. Vis. 2013; 19:1848-1851)."
Nature Publishing Group (NPG), includes but not limited to:
Excerpt from Guidelines: Nature has a “Reporting Checklist for Life Sciences Articles” that includes the following under the topic of “Reagents”: "7. Cell line identity: a. Are any cell lines used in this paper listed in the database of commonly misidentified cell lines maintained by ICLAC (also available in NCBI Biosample)? b. If yes, include in the Methods section a scientific justification of their use – indicate here on which page (or section and paragraph) the justification can be found. c. For each cell line, include in the Methods section a statement that specifies:
- the source of the cell lines
- have the cell lines been authenticated? If so, by which method?
- have the cell lines been tested for mycoplasma contamination? In this checklist, indicate on which page (or section and paragraph) the information can be found."
Excerpt from Guidelines: "Methods and Materials: If cell lines are used, include a statement that addresses:
Society for Endocrinology Publications
Excerpt from Guidelines: “We require that all cell lines are authenticated for correct origin."
Excerpt from Guidelines: "Authors should check established cell lines using the ICLAC Database of Cross-contaminated or Misidentified Cell Lines to confirm they are not misidentified or contaminated. Cell line authentication is recommended - e.g. by karyotyping, isozyme analysis, or short tandem repeats (STR) analysis - and may be required during peer review or after publication."
The Open Breast Cancer Journal (Bentham Open)
Excerpt from Guidelines: "Bentham OPEN recommends that all cell lines be authenticated prior to submitting a paper for review. ...Authentication is required when a new line is established or acquired, before freezing a cell line, if the performance of the line is not consistent or results are unexpected, if using more than one cell line, and before publication of the study."