Misidentified cell lines: failures of peer review, varying journal responses to misidentification inquiries, and strategies for safeguarding biomedical research

Abstract

Background

Continuous cell lines are indispensable in basic and preclinical research. However, cross-contamination, misidentification, and over-passaging affect the validity and reproducibility of biomedical results. Although there have been efforts to highlight this problem for decades, definitive prevention remains a challenge. The International Cell Line Authentication Committee (ICLAC) registry (version 13, 26 April 2024) lists nearly 600 misidentified or contaminated cell lines. The inappropriate use of such cells has led to countless publications containing invalid data, creating a ripple effect of wasted resources, misleading follow-up studies, and compromised evidence-based conclusions.

Methods

The ICLAC registry was consulted to identify commonly misidentified cell lines. A literature search of PubMed was performed to identify recent papers using these lines in liver-related experiments. Four publications with questionable conclusions were highlighted, and the editors of the respective journals were informed with short comments or letters to the editor.

Results

Reactions from journal editors varied widely. In two cases, the editors quickly published the comments, resulting in transparent corrections. In the third example, the editor conducted an internal investigation without immediately publishing a correction. In the fourth example, the journal declined to address concerns publicly.

Conclusions

Misidentified cell lines pose an ongoing threat to scientific rigor. Despite some responsible editorial interventions, the lack of universal standards fosters the dissemination of erroneous data. However, authors, reviewers, and editors have some important tools to prevent publications with misidentified cells by consulting available resources (e.g., ICLAC, Cellosaurus, Research Resource Identification Portal, SciScore™), and adopting consistent procedures to maintain research integrity.

Introduction

Cell misidentification and cross-contamination undermine the validity and reliability of biomedical research [1, 2]. If the cells used in an experiment do not truly represent the intended tissue or species, the data generated may be irreproducible or biologically misleading [3, 4]. Despite long-standing awareness of this problem, numerous studies, possibly numbering in the tens of thousands, have used lines that are either contaminated with other cells or mislabeled [1, 2, 5].

The International Cell Line Authentication Committee (ICLAC) has been instrumental in highlighting and monitoring such misidentifications. Their regularly updated register (current version 13, 26 April 2024) lists 593 misidentified or cross-contaminated lines [5, 6]. One of the most common contaminants is the HeLa cell line, due to its prolific growth capacity. Because HeLa contamination spreads undetected, lines purporting to represent the liver, stomach, or other tissues may in fact be predominantly HeLa.

Researchers who unwittingly rely on such misidentified lines may draw incorrect conclusions not only about disease mechanisms, drug responses, and gene regulation, but also about broader physiological processes. This problem potentially undermines the reproducibility of published data, stalls scientific progress and jeopardizes the development of future therapies for diseases such as cancer. Cell authentication efforts, short tandem repeat (STR) profiling, morphological verification, and searching resources such Cellosaurus are increasingly recommended or even required by many journals and funding agencies [3, 4]. Unfortunately, there is a fundamental lack of understanding among researchers that only authenticated cells provide robust scientific results, and also among editors in dealing with papers that were generated with misidentified cells. This article discusses four examples of how editors have dealt with such papers and offers strategies for avoiding publication of such data.

Methods

Selection of misidentified cell lines

The ICLAC register of known misidentified cell lines (version 13) was screened for cell lines commonly used as models to study gastrointestinal diseases. The search yielded a large number of cells from which the following HeLa contaminated or HeLa derived cells were selected for further investigation: QGY-7703 (also known as QGY7703 or QGY), BGC-823 (also known as BGC823), BEL-7402 (also known as BEL7402), L-02 (also known as L02, LO2, HL-7702, HL7702, Liver-02, or Human Liver-7702), and WRL 68 (also known as WRL-86 or WRL68).

Literature search

The PubMed database was searched for recent articles using these cell lines in liver-related research. Search terms included (i) “QGY-7703 or QGY”, (ii) “BGC-823 or BGC823”, (iii) “BEL-7402 or BEL7402”, (iv) “WRL-68 or WRL68”, and (v)"L02 cells"or"LO2 cells"or HL-7702 or HL7702 or Liver-02 or"Human Liver-7702". Priority was given to papers published in 2025 whose conclusions relied heavily on the erroneous assumption of derivation from a liver cell. From the large number of papers, four papers were finally selected.

Identification of responsible editors

For each paper identified, offices of the journals were contacted via a letter to the editor or a comment submission. The approach to each journal was consistent: we briefly documented the misidentification of the cell line(s), provided the ICLAC and other references, and explained how this problem undermined the core findings of the paper.

SciScore™ search

The complete Methods section from Example 4 (see below) starting with “Methods Data source to on the same real-time fluorescence quantitative PCR system (StepOnePlus) was copied and pasted into SciSore™’s methods submission tool. The results of the.zip file obtained were unzipped and the reports copied into a PDF file.

Results

Overview of identified misidentified cell lines

To identify misidentified cell lines, the most recent ICLAC registry, which currently lists 593 cell lines, was screened. A total of 21 “liver cell lines” and 14 “stomach cell lines” were listed as misidentified or cross-contaminated in the register (Table 1). From the listed cell lines, the cell lines QGY-7703, BGC-823, BEL-7402, L-02, and WRL-68 were selected to identify relevant publications in the PubMed database because they are still widely used as cell culture models in the field of liver research. A comprehensive search of the PubMed database identified almost 6,000 publications using the misidentified cell lines QGY-7703, BGC-823, BEL-7402, L-02, and WRL-68 (Table 2). This search used the specific names of these cell lines as keywords, in some cases combined with other relevant terms, to retrieve the widest possible range of studies.

Table 1.

Misidentified or cross-contaminated cell lines listed in the ICLAC registry that are commonly used in gastrointestinal research areas¹

Misidentified cell line	Registration ID	Claimed Species	Claimed cell type	Contaminating cell line	Actual species	Actual cell type
BEL-7402	ICLAC-00549	Human	Liver, hepatocellular carcinoma	HeLa/HCT 8	Human	Cervical adenocarcinoma/colon carcinoma
BEL-7404	ICLAC-00550	Human	Liver, hepatocellular carcinoma	HeLa	Human	Cervical adenocarcinoma
Chang liver	ICLAC-00002	Human	Liver, normal hepatic cells	HeLa	Human	Cervical adenocarcinoma
D-11 (R1 derivative)	ICLAC-00582	Rainbow trout, Oncorhynchus mykiss	Liver, normal hepatic cells	Unknown	Chinook salmon, Oncorhynchus tshawytscha	Unknown
GREF-X	ICLAC-00123	Human	Liver, hepatic myofibroblast	Unknown	Rat, Rattus norvegicus	Unknown
H7D7 A	ICLAC-00203	Human	Liver, normal cells (SV40-transformed)	HepG2	Human	Liver, hepatoblastoma
H7D7B	ICLAC-00204	Human	Liver, normal cells (SV40-transformed)	HepG2	Human	Liver, hepatoblastoma
H7D7BD5 (H7D7B derivative)	ICLAC-00560	Human	Liver, normal cells (SV40-transformed)	HepG2	Human	Liver, hepatoblastoma
H7D7 C	ICLAC-00205	Human	Liver, normal cells (SV40-transformed)	HepG2	Human	Liver, hepatoblastoma
H7D7D	ICLAC-00206	Human	Liver, normal cells (SV40-transformed)	HepG2	Human	Liver, hepatoblastoma
Hepa-T1	ICLAC-00567	Nile tilapia, Oreochromis niloticus	Liver, normal hepatic cells	Unknown, possibly Hepa-E1	Japanese eel, Anguilla japonica	Unknown
HuL-1	ICLAC-00318	Human	Liver, hepatocellular carcinoma	HeLa	Human	Cervical adenocarcinoma
ImKC	ICLAC-00620	Mouse, Mus musculus (H-2 K(b)-tsA58 transgenic line)	Liver, normal Kupffer cells	RAW 264.7	Mouse, Mus musculus	Macrophage, transformed
L-02	ICLAC-00575	Human	Liver, normal hepatic cells	HeLa	Human	Cervical adenocarcinoma
QGY-7703	ICLAC-00552	Human	Liver, hepatocellular carcinoma	HeLa	Human	Cervical adenocarcinoma
QGY-7703	ICLAC-00552	Human	Liver, hepatocellular carcinoma	HeLa	Human	Cervical adenocarcinoma
QSG-7701	ICLAC-00553	Human	Liver, normal hepatic cells	HeLa	Human	Cervical adenocarcinoma
R1	ICLAC-00581	Rainbow trout, Oncorhynchus mykiss	Liver, normal hepatic cells	Unknown	Chinook salmon, Oncorhynchus tshawytscha	Unknown
RBHF-1	ICLAC-00155	Human	Liver, hepatoma	Unknown	Unknown, not human	Unknown
SMMC-7721	ICLAC-00554	Human	Liver, hepatocellular carcinoma	HeLa	Human	Cervical adenocarcinoma
WRL 68	ICLAC-00351	Human	Liver, embryonic cells	HeLa	Human	Cervical adenocarcinoma
2474/90	ICLAC-00107	Human	Gastric carcinoma	HT-29	Human	Colon carcinoma
2957/90	ICLAC-00108	Human	Gastric carcinoma	HT-29	Human	Colon carcinoma
3051/80	ICLAC-00109	Human	Gastric carcinoma	HT-29	Human	Colon carcinoma
AZ521	ICLAC-00369	Human	Gastric carcinoma	HuTu 80	Human	Duodenal carcinoma
BGC-823	ICLAC-00570	Human	Gastric carcinoma	HeLa	Human	Cervical adenocarcinoma
CaVe	ICLAC-00036	Human	Gastric carcinoma	HeLa	Human	Cervical adenocarcinoma
GT3 TKB	ICLAC-00202	Human	Gastric carcinoma	RERF-LC-A1	Human	Lung carcinoma
Hs 677.St	ICLAC-00401	Human	Gastric tissue, normal	Unknown	Mouse, Mus musculus	Unknown
HSC-41	ICLAC-00312	Human	Gastric carcinoma	HSC-42	Human	Gastric carcinoma
MGC-803 (MGc80-3)	ICLAC-00588	Human	Gastric carcinoma	Hybrid, HeLa/unknown	Human	Hybrid, cervical adenocarcinoma/unknown
MKN28	ICLAC-00328	Human	Gastric carcinoma	MKN74	Human	Gastric carcinoma
NS-3	ICLAC-00336	Human	Gastric carcinoma	COLO 201	Human	Colon carcinoma
OCUM-6	ICLAC-00337	Human	Gastric carcinoma	OCUM-11	Human	Gastric carcinoma
SGC-7901	ICLAC-00577	Human	Gastric carcinoma	HeLa	Human	Cervical adenocarcinoma

¹All information taken from [6]

Table 2.

Use of cell lines QGY-7703, BGC-823, BEL-7402, L-02, and WRL-68 in biomedical research¹

Cell line	Identified as	Actual or contaminating cell type	Search term in PubMed	Number of hits in PubMed
QGY-7703	Hepatoma cell line derived from a 35-year-old female patient [7]	HeLa contaminated [8, 9]	“QGY-7703” or “QGY cells”	138
BGC-823	Gastric adenocarcinoma induced by diallyl trisulfide [10]	HeLa contaminated [9, 11, 12]	“BGC-823 or BGC823”	1,688
BEL-7402	Hepatocellular carcinoma cell line established from an operated 53-year-old man with hepatocellular carcinoma [13]	HeLa contaminated [8, 9, 11, 12]	“BEL-7402 or BEL7402”	1,742
L-02	Fetal hepatocyte cell line [14]	HeLa contaminated [11, 12]	"L02 cells"or"LO2 cells"or HL-7702 or HL7702 or Liver-02 or"Human Liver-7702"	2,091
WRL-68	Fetal liver epithelial cell line [15]	HeLa derived [16, 17]	"WRL-68 or WRL68"	268

¹The PubMed search was carried out on 25 March 2025

From all these papers four recent papers were selected that reported questionable findings on liver cell function from these cells and/or suggested potential therapeutic options from them. Due to the questionable nature of the reported findings, commentaries or editorials were written to the journals that published these questionable studies to ensure that the scientific community was made aware of the misidentification and its implications. The following is a discussion of how these commentaries/editorials were handled by the journals. In addition, it is discussed what we can learn and how authors and editors can prevent the publication of falsified data resulting from the use of misidentified cells.

Example 1: Misidentification of cell line QGY-7703

In the first example, the authors used the QGY-7703 cell line (believed to be a true hepatocellular carcinoma line) [18]. The authors used rhaddeanin A, the main active compound derived from Anemonoides raddeana (Regel) Holub, and tested the inhibitory effect of this drug on QGY-7703 cells. Based on the experiments, the authors concluded that this drug induces 5 methylcytosine DNA modification by downregulating DNMT3 A and DNMT3B in hepatocellular carcinoma and exerts a therapeutic effect by inhibiting tumor metastasis and promoting cellular apoptosis, attributing a significant activity of rhaddeanin A against hepatocarcinoma [18]. As QGY-7703 is in fact HeLa contaminated (ICLAC-00552), the conclusions regarding “hepatoma-specific” drug activity are likely invalid. A short commentary was submitted to the journal indicating this fact. The journal dealt with it promptly, sent it out for peer review and published it shortly afterwards [19]. Their quick action underlines their transparency and editorial accountability.

Example 2: Triple misidentification (BGC-823, BEL-7402, and HL-7702)

One paper used BGC-823 and BEL-7402 cells (both contaminated with HeLa cells) and tested the biological effects of new quinolone-based derivatives in comparison to HL-7702 (i.e., L-02) cells that are also contaminated with HeLa cells [20]. Based on their findings, the authors concluded that these compounds exhibit selective toxicity against “gastric” or “hepatoma” cells while sparing “normal” liver cells [20]. A short commentary submitted to the journals was accepted [21] and the authors were invited to respond [22]. This proactive, back-to-back publication of commentary and author response underscores exemplary scientific discourse.

Example 3: Misidentification of cell line WRL-68

Another article attributed results from WRL-68 cells to “human liver cells” and concluded that an organophosphate pesticide could transform normal liver cells into a malignant phenotype [23]. Following a letter to the editor pointed pointing out that WRL-68 was in fact HeLa (ICLAC-00351), the editor refused to publish the letter but launched a private investigation under the guidelines of the Committee on Publication Ethics (COPE). No public clarification has yet been issued. Nevertheless, the letter was published as a preprint, highlighting the incorrect use of cells in the paper presented [24].

Example 4: Misidentification of cell line L-02

A study comparing L-02 (“normal liver”) cells with Huh7 concluded that differential expression of key histone lactylation genes may be relevant to hepatocellular carcinoma [25]. As L-02 is derived from HeLa, these data are suspect. A letter to the journal pointing out the misidentification was rejected, and the journal indicated that the letter was out of scope and would not proceed further. Subsequent attempts to follow up remained unanswered. Therefore, the concerns were instead published as a preprint [26].

Discussion

Misidentified cell lines and their far-reaching impact on biomedical research

Cell line misidentification is widely recognized as a major problem in biomedical research. A conservative estimate suggests that 32,755 studies have used misidentified cells, which in turn have been cited in approximately half a million subsequent publications [27]. Another, more recent estimate suggests that 8.6% of all cell lines in use are misidentified [28]. In addition, approximately 5% of human cell lines referenced in peer-reviewed manuscripts appear to be misidentified [3]. Currently, the ICLAC registry documents nearly 600 cell lines confirmed to be misidentified due to cross-contamination or other factors, further illustrating the magnitude of this problem [6].

The present study highlights the persistent and pressing problem in biomedical research, the unsuspecting use of misidentified or cross-contaminated continuous cell lines. Despite long-standing awareness of the problems associated with cell line authentication, the problem remains widespread and even reputable journals inadvertently publish invalid research. A key factor perpetuating this problem is the extensive historical use of certain lines, such as QGY-7703, BGC-823, BEL-7402, L-02, and WRL-68, ostensibly for modeling liver and stomach pathophysiology, when in fact they are derived from, or contaminated with, HeLa cells. As HeLa is an immortal line with high proliferative capacity, any inadvertent cross-contamination can profoundly undermine the defining characteristics of the original cell line.

Cell misidentification remains a growing problem, as evidenced by the increasing use of questionable cell lines in published papers. For example, a PubMed search using the terms “Lo2 cells” or “L-O2” returned 263 results on 27 July 2022 [29], and by 25 March 2025, this number had risen to 666. Such statistics underline the continuing increase in references to potentially misidentified cell lines and highlight the urgent need for more stringent validation measures.

Need for strengthening editorial standards

The four examples presented here illustrate significant differences in peer review standards and editorial decisions. On the one hand, there are journals whose editorial teams directly acknowledge errors and swiftly move quickly to correct the scientific record. In the first example, the handling of a misidentified cell line demonstrates the positive outcome of a proactive editorial policy and willingness to publish a correction note. Similarly, in the second example, the journal not only accepted criticism of a paper’s questionable results, but also provided an opportunity for the original authors to respond. This open dialogue illustrates how constructive peer review and transparent editorial processes can reduce the risk of invalid results being disseminated.

On the other hand, the third and fourth examples emphasize that not all journals adhere to such strict standards. Although, as in the third example, some editorial teams deal with concerns privately in accordance with the COPE guidelines, the lack of a transparent publication record may prevent widespread awareness that a particular article contains critical methodological flaws. In the fourth example, a journal’s unwillingness to accept discussions about cell misidentification, by arguing that a letter to the editor does not fit the journal’s article types of the journal, not only calls into question the journal’s editorial practices, but also points to a wider systemic shortcoming: many journals do not have formal processes for handling comments or concerns about published work. This gap ultimately risks undermining trust between readers and researchers.

The persistence of misidentified cell lines in published research not only undermines the validity of individual studies, but also poses a broader challenge to reproducibility within the scientific community. It is evident that despite existing guidelines and registries, such as those provided by the ICLAC, many researchers remain unaware of or indifferent to these critical issues. This gap highlights the urgent need for increased training and awareness among editors, reviewers, and authors alike regarding proper cell line authentication practices.

The consequences are far-reaching. First, the use of misidentified lines can directly lead to invalid or irreproducible results, thus hindering scientific progress [3]. Second, scientists who rely on these erroneous data in follow-up studies divert time, money and effort away from more promising lines of inquiry [27]. Finally, the continued publication of papers using such lines can undermine public confidence and hinder the development of scientifically sound therapies, particularly for serious diseases such as cancer, where preclinical models and evidence need to be as accurate and reliable as possible [30].

Strategies for authors to prevent usage of misidentified cells

Authentication steps such as short tandem repeat (STR) profiling and mycoplasma testing, while widely advocated [3, 4], are still not uniformly required by all journals. In addition, editorial boards, reviewers, and authors sometimes inadvertently assume the authenticity of commercially available lines, trusting that suppliers have performed due diligence.

Interestingly, authors using Research Resource Identifiers (RRIDs) in their work seem to be more aware of the problem of cell line misidentification. Their publications show a significantly lower incidence of the use of misidentified cells, probably because the authors are required to check the RRID syntax against a central database. This process includes warning messages, such as the ICLAC notice, which are similar to the warnings found in Cellosaurus [28]. This suggests that using the RRID portal before starting with experiments is a good way to avoid the use of misidentified cells and the production of falsified data. If the authors of the four cases described here had used the RRID portal, they should have noticed that the cell lines used in their studies were listed as contaminated in the RRID portal (Table 3, Fig. 1).

Table 3.

Information in the RRID portal on QGY-7703, BGC-823, BEL-7402, L-02, and WRL-68¹

Cell line	RRID Identification no	Remark	Link with documentation
QGY-7703	RRID:CVCL_6715	Contaminated	https://www.cellosaurus.org/CVCL_6715
BGC-823	RRID:CVCL_3360	Contaminated, Discontinued	https://www.cellosaurus.org/CVCL_3360
BEL-7402	RRID:CVCL_5492	Contaminated	https://www.cellosaurus.org/CVCL_5492
L-02	RRID:CVCL_6926	L-02	https://www.cellosaurus.org/CVCL_6926
WRL-68	RRID:CVCL_0581	Contaminated, Discontinued	https://www.cellosaurus.org/CVCL_0581

¹All information was taken from the [31]

Fig. 1.

Research Resource Identifier information provided by the RRID portal for cell line L-02 (RRID:CVCL_6926). The representative information requested for L0-2 in the RRID portal indicates that this cell line is contaminated. The portal also allows additional information (references, sex, category, vendor, mentions, issues status, and issues types) to be obtained, by clicking on the tabs in the left sidebar. Most importantly, there is a link to the Cellosaurus database, which provides detailed information on each cell line. Screenshot taken from [https://rrid.site/data/source/SCR_013869-1/search?q=Lo2&l=Lo2].

Importantly, the RRID is linked to the Cellosaurus database, which provides further details of each cell line, including cell synonyms, cell provider, STR profile data, relevant publications, and other useful information (Fig. 2).

Fig. 2.

Information provided by the Cellosaurus database for a representative cell line. Shown is the information provided by the Cellosaurus database for L-02, which provides detailed information about this cell line. Useful publications, web papers, cell line providers, and much more are available at a glance. The most important information is the STR profile, which is useful for authors authenticating this line. The screenshot is taken from [https://www.cellosaurus.org/CVCL_6926]

Importantly, cell line authentication can be achieved using relatively simple and accessible methods that increase the reliability of research. One common approach is STR profiling, which analyses specific regions of DNA to create a unique genetic fingerprint for each cell line [32]. STR profiling is widely available and can be performed using commercial kits that provide clear protocols for researchers. In this context, the Cellosaurus database is an invaluable resource for researchers working with cell lines, providing comprehensive information on over 40,000 different cell lines [33, 34]. It contains detailed data on cell line origin, characteristics, authentication status, and STR profiles, making it an essential tool for verifying the identity of cell lines used in research. It also provides services such as the Cellosaurus STR Similarity Search Tool (CLASTR), which allows comparison of STR profiles obtained from human, mouse, and canine cells to be compared with those available in the Cellosaurus cell line knowledge resource [35, 36].

By providing insight into potential misidentifications and cross-contamination, Cellosaurus helps researchers make informed decisions and ensure the integrity of their experimental results. In addition, its user-friendly interface provides easy access to critical information, facilitating better cell culture practices and improving the overall quality of research. Similarly, morphological assessment, the observation of the physical characteristics of cells under a microscope, can help to identify discrepancies in cell lines [37]. In addition, the expression of specific markers can help to authenticate for cell lines. In addition, online databases such as the ICLAC provide valuable resources for researchers to identify misidentified cell lines. By implementing these simple techniques, researchers can significantly reduce the risk of working with misidentified cell lines and contribute to more accurate and reproducible scientific results. Therefore, cell line authentication is essential and has many benefits in preventing the far-reaching consequences of cell misidentification (Fig. 3). Ultimately, these strategies will help researchers to significantly improve the quality of scientific research. This commitment to rigorous authentication fosters trust in the scientific community by maintaining the integrity of research results and promoting reproducibility across studies.

Fig. 3.

Flowchart of the cell line authentication process and consequences of misidentification. This flowchart outlines the key steps involved in the cell line authentication process and the potential consequences of misidentified or contaminated cell lines. It starts with"cell line selection"and progresses through four key authentication steps: selecting the cell line and collecting cell line information, obtaining the cell line from a reliable source, performing authentication tests (such as STR profiling and morphological assessment), and comparing the results with the Cellosaurus database [34, Cellosaurus]. This is followed by a decision point that determines whether the cell line is authenticated or misidentified/contaminated. If authenticated, researchers can continue to use the cell line in their research, but if misidentified, the researcher should identify another suitable cell line model. The consequences of misidentification are far-reaching, consequences leading to problems with invalid research results, wasted resources (time, money, effort) and compromised patient safety. Ultimately, it leads to a loss of research credibility and often requires the correction or even retraction of published papers

In this context, it is worth noting that SciScore™ (SciCrunch, San Diego, USA) that is an online service supported by many governments, foundations, funding agencies, industry partners, and publishers, and similar automated tools can help detect misidentified cell lines by scanning submitted manuscripts for key indicators of cell line authentication. SciScore™ is an online tool that can scan the Materials and Methods section of a submitted paper for a variety of rigor criteria relevant to contributing to the reproducibility of scientific research [38]. Specifically, it analyzes the description of research resources such as antibodies, cell lines, plasmids, and software tools. Based on the information provided in the paper, SciScore™ generates a reproducibility score for the paper on a scale of 1 to 10, based on the expectation that a method section of a paper should include information on catalog numbers and RRIDs, which can be considered as universal product codes that allow the identification of specific compounds required for an experiment [39].

Moreover, authors and reviewers can search for unique cell line identifiers, such as those provided by Cellosaurus, which is a comprehensive cell line knowledge resource that provides detailed information on thousands of cell lines, including their intended origin, known contaminants, and authentication data such as STR profiles. By referencing Cellosaurus during manuscript preparation or peer review, authors, editors, and reviewers can confirm the identity of a line and check for known misidentifications. This proactive verification greatly reduces the risk of publishing studies that inadvertently use contaminated or misidentified cells, thus promoting higher standards of research integrity.

Similarly, the ICLAC registry provides a regularly updated list of misidentified and cross-contaminated cell lines, highlighting their origin, known contaminants, and correct names. By checking this registry before designing experiments or reviewing manuscripts, researchers and editors can quickly identify potential problems related to the true identity of a given cell line, thereby improving the overall integrity and reproducibility of biomedical research.

More importantly, editors should require authors to have documented authentication methods, such as STR profiling, when using immortalized cell lines in their study. By flagging missing information or potential discrepancies in real time, it will be possible to avoid the risk of publishing research based on misidentified or contaminated lines, which will also help to enhance a journal’s reputation. Therefore, there should be a clear strategy for researchers using immortalized cell lines in their study. Before starting experiments, researchers should verify the authenticity of their cell lines by cross-referencing resources such as the ICLAC database, Cellosaurus, BioSample database, and ensuring that they have the correct RRID information (Table 4).

Table 4.

Useful resources for the prevention of the use of misidentified cells

Resource	Remark	Information given	Link to resource	References
ICLAC (Register of misidentified cell lines)	The ICLAC is an independent committee that curates a registry of cell lines that are known to be misidentified through cross-contamination or other means	The latest version of the register (version 13, released 16 April 2024) lists 593 cell lines	https://iclac.org/databases/cross-contaminations/	[16]
Cellosaurus (Cell line encyclopedia)	Cellosaurus is a comprehensive database dedicated to cataloguing cell lines used in biomedical research, covering both vertebrate and invertebrate species	The latest version of the cell line database (release 51, December 2024) lists 161,202 cell lines from various species, including 119,920 from human, 28,720 from mouse, and 2,999 from rat origin	https://www.cellosaurus.org/	[34]
Research Resource Identifiers (RRID)	The RRID project aims to improve the way research resources are identified, discovered, and re-used. By promoting more accurate citation of biological materials, it helps to address challenges to reproducibility, efficiency, and connectivity that result from imprecise or inconsistent referencing	The RRID initiative, first launched in February 2012, provides information on antibodies, plasmids, organisms, cell lines, tools, core facilities, and many other biosamples	https://rrid.site/	[39]
National Library of Medicine (BioSample database)	The NCBI BioSample database contains descriptive details of the physical biological materials used to generate data for NCBI’s major data repositories	This database contains information about the physical biological materials, such as cell lines, tissue biopsies, or environmental isolates, used to generate data for various NCBI repositories. Each record contains structured attributes detailing sample properties, origin and standardized attribute names, and these records are linked to published data and associated BioProjects	https://www.ncbi.nlm.nih.gov/biosample	[40]
SciScore™	SciScore is an automated text-mining tool that helps authors and journals easily assess scientific manuscripts for reporting compliance	It checks for important methodological details, identifies missing information such as antibodies, cell lines, and organism, and supports the transparency and reproducibility of research studies. Missing RRID suggestions are provided in the output file	https://sciscore.com/	[38, 41]

Expert reviewers and editors could use the SciScore™ routine to score papers by checking for the presence and correctness of several unique identifiers, including RRIDs. If cell lines are detected in the Materials section, further checks can be made to ensure that the authors have carried out cell line authentication, cell line contamination checks and have provided information on company or source information, catalogue number, and RRID from Cellosaurus [42]. As mentioned above, the SciScore™ assigns papers a rating score from 1 to 10 to papers based on both rigor and compliance. However, as of 22 March 2025, the price to use this software is USD 39.99 for academic authors and USD 49.99 for corporate authors for 3 credits, which allows the submission of three papers [43].

Importantly, SciScore™’s evaluation of 1,578,964 articles for rigor criteria showed that the average annual score that has doubled from 2.0 ± 0.9 to 4.2 ± 1.7 between 1997 and 2019, suggesting that the calls for improved scientific reporting since the early 2000 s have borne fruit [38]. SciScore™ also recommends that cell lines should be authenticated according to the ICLAC committee guidelines, most likely by STR profiling, which is recommended at the beginning of the experiment, at the end of the experiment and at a random time during the experiment [38]. In this context, it is worth mentioning that a systematic analysis of 2,280 journals with more than 180,316 articles and more than 388,337 cell lines showed that the percentage of reporting the authentication of the cell line used varied different, ranging from 0 to 71% [38].

Strategies for strengthening editorial standards

The four examples presented illustrate a spectrum of editorial responses to the identification of invalid data resulting from the use of misidentified continuous cell lines (Table 5). While some journals demonstrated a commendable commitment to correcting errors and maintaining rigorous standards, one journal showed a worrying lack of responsiveness and accountability.

Table 5.

Summary of activities following receipt of Commentary/Letter to the Editor

	Case 1	Case 2	Case 3	Case 4
Action 1	Comment forwarded to reviewers	Comment provisionally accepted	Letter initially rejected with invitation for direct communication	Letter rejected due to scope issues
Action 2	Review completed and minor revision requested	Authors given the opportunity to respond	Direct email sent to Lead Editor	Lack of communication from the editor
Action 3	Commentary accepted and published	Both articles will be published back-to-back	Investigation initiated based on concerns raised	Failure of the editorial team and editor to address the concerns raised
Outcome	The journal and its editors demonstrated their commitment to scientific standards by promptly addressing the concerns raised in the Commentary/Letter to the Editor. Their commitment to transparency and thorough evaluation helped to strengthen trust within the scientific community and to maintain high standards of research integrity		The journal's dismissal of the concerns raised in the Commentary/Letter to the Editor suggests a failure to uphold scientific standards. This lack of responsiveness not only undermines trust in the scientific community, but also casts significant doubts on the journal's commitment to research integrity and rigorous peer review
Diverse responses reflect editorial commitment and challenges in dealing with misidentified cell lines

In research, it is important to foster an environment where constructive feedback is welcomed and addressed promptly. Consequently, editorial policies should prioritise transparency and engagement with legitimate concerns raised by peers in order to maintain confidence in the published literature. Journals need to ensure that their processes are equipped to handle critical enquiries effectively, as neglecting this responsibility can have a significant impact on scientific progress.

This study serves as a call to action for journal editors and peer reviewers to adopt more stringent measures when evaluating manuscripts involving cell lines. By prioritising rigorous peer review processes that include thorough verification of cell line authenticity, we can collectively work towards improving the reliability of biomedical research results. It is imperative that we strive for excellence in scientific publishing, where accuracy trumps expediency, to ensure the future of research integrity and patient safety. Undoubtedly, strict journal requirements for the provision of appropriate data help to prevent the use of misidentified cells and the consequent risk of drawing erroneous conclusions [4]. If a paper with a misidentified cell line has already been published and is identified after publication, authors can issue corrigenda or retractions to correct the scientific record, readers can alert the journal with comments or letters outlining the problems, and editors can investigate the extent of the error and determine whether corrections or retractions are warranted.

However, despite robust authentication practices and verification tools, including databases such as Cellosaurus, registries such as that from ICLAC, and automated screening services such as SciScore™, there is still no absolute guarantee against the publication of papers based on misidentified or contaminated cell lines. Limitations such as incomplete reporting, delayed awareness of new misidentifications, and human or technical error can allow errors to slip through even the most rigorous review processes. For example, SciScore™ scoring of the full Materials and Methods section of the paper discussed as example 4 (performed on 22 March 2025) resulted in an overall score of 5.0, which is the 81 st percentile of all papers included in the PubMed Central (PMC) archive and higher than the average score of 4.2 that was reported for papers listed in PubMed in the year 2019 [38]. Importantly, the report (Suppl. File 1) identified the Huh7 control cells used in the discussed study as a cell line and suggested adding the correct RRID identifier number (RRID-CVCL-0336), but failed to identify the L-02 cell line, most likely because this cell line was referred to by its alias name L02, which has the RRID identifier number RRID:CVCL_6926.

Consequently, while these measures significantly reduce the likelihood of invalid research entering the literature, there remains a residual risk of misidentified cells influencing scientific conclusions. It should be noted that the COPE guidelines, first established in 1997, provide a framework for editors and publishers to address issues of research and publication integrity, including concerns about misidentified or contaminated cell lines. Although the COPE recommendations do not specifically mandate cell line authentication procedures, they do provide clear guidance on how to handle potential errors or misconduct that arise after publication. If editors become aware of misidentified cells used in a published study, the COPE guidelines encourage a thorough investigation, based on clear communication with the authors and, if necessary, publication of a correction or retraction. In addition, if a published paper is subsequently found to contain major errors, editors must take responsibility for correcting the record prominently and promptly [44]. The COPE guidelines also recommend that journals to have policies for responding to institutions and other organizations that investigate cases of research misconduct [45].

It should be noted that you could also criticize the experts who have initially reviewed the papers. Unfortunately, they did not request or investigate information about the cell line used, which would have been essential to prevent the publication of inaccurate research data. It must also be acknowledged that the authors may have used the misidentified cells in good faith. Some companies sell these cells under different labels and often overlook information about their misidentification. This does not imply malicious intent on the part of the researchers.

What need to be done?

Going forward, it is essential that journals adopt comprehensive cell line authentication policies. Such policies could include (i) requiring mandatory documentation of authentication for all submitted manuscripts involving cell lines, (ii) increased training of editors and reviewers so that they are aware of the existence of the ICLAC registry and related databases, and (iii) the establishment of robust mechanisms for publishing concerns or corrections, such as brief comments, letters to the editor, or formal corrigenda, if the use of misidentified cell lines is discovered after publication. In parallel, authors should be made aware of online resources, including regularly updated registries such as ICLAC, and trained to perform or request regular quality checks of their cell lines.

In addition, commercial biotech vendors and cell culture banks play a critical role in either perpetuating or preventing the spread of misidentified cells. When companies prioritize profit over thorough authentication practices, they risk distributing contaminated or misrepresented lines that can compromise the validity of countless research projects. At the same time, reputable cell culture banks that enforce strict verification protocols and quality controls, serve as an essential safeguard by ensuring that the cells they provide meet strict standards of identity and purity [46]. By maintaining transparent documentation, encouraging regular testing, and actively updating records of known misidentified lines, these institutions can help maintain the integrity of the scientific endeavor and foster confidence in biomedical research. Ultimately, even in situations where cell misidentification is not initially identified during peer review, these efforts help editors maintain scientific rigor and confidence in the scientific record.

Limitations of this study

A notable limitation of this research paper is that the discussion relies on only four case examples to illustrate journal responses to misidentified cells, which may not comprehensively represent the range of editorial practices across the scientific publishing landscape. Additionally, the study necessarily relies on publicly visible editorial decisions and the author’s personal experience, rather than a systematic sample of all published cases, which may introduce an inherent selection bias. The paper is further limited by its focus on a handful of commonly used misidentified cell lines, leaving open the possibility that less common lines or different areas of research may show alternative patterns of cell misidentification or editorial responses. Furthermore, the paper does not provide robust quantitative or statistical analyses that could quantify the impact of these editorial practices on reproducibility across journals, limiting the generalizability of its conclusions. Finally, although the author acknowledges that many researchers may use misidentified lines in good faith, the paper largely does not address the complexities of establishing intent or the extent to which commercial suppliers and other intermediaries influence misidentification, highlighting the need for broader investigations into the roles of all stakeholders in maintaining cell line authenticity.

Conclusion

In conclusion, this paper reaffirms that prompt editorial responses to concerns about misidentification, even after publication, are a cornerstone of scientific integrity. While some editorial teams have demonstrated commendable rigor and transparency, others have not. The implementation of universal authentication standards and open avenues for comment are critical if the research community is to minimize the continued use of invalid cell lines. Many authors publish erroneous results based on misidentified cell lines simply because they are unaware of the contamination or mislabeling, rather than acting deliberately. In most cases, researchers trust the provenance of the material they receive from colleagues, suppliers, or from cell culture banks, and do not suspect that the lines may be of limited use. This unintentional oversight highlights the importance of implementing robust and standardized authentication procedures to ensure the validity of research results. Ultimately, addressing the issue of misidentification will enhance the reproducibility and credibility of biomedical research, thereby ensuring that scientific effort and resources are invested wisely to truly advance knowledge and improve patient care. If journals do not respond to comments made to alert them to the use of misidentified cells, options include submitting a comment to a preprint server, posting comments on PubPeer, or informing the STM Research Integrity Group.

Abbreviations

CLASTR

Cellosaurus STR Similarity Search Tool

COPE

Committee on Publication Ethics

ICLAC

International Cell Line Authentication Committee

RRID(s)

Research Resource Identifier(s)

STR

Short Tandem Repeat

Authors’ contributions

R.W.: Conceptualization and manuscript writing.

Funding

The laboratory of the author is supported by grants from the German Research Foundation (project WE2554/17–1), the German Cancer Aid (grant 70115581), and a grant from the Interdisciplinary Centre for Clinical Research within the Faculty of Medicine at the RWTH Aachen University (grant PTD 1–5).

Data availability

Data sharing does not apply to this article. No data sets were generated or analyzed during the current study.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The author declares that he has no competing interest. However, he would like to mention that he is a member of the ICLAC committee, which aims to increase the visibility of false or misidentified cell lines in biomedical research.