Discovery of HeLa Cell Contamination in HES Cells: Call for Cell Line Authentication in Reproductive Biology Research

Kniss, Douglas A.; Summerfield, Taryn

doi:10.1177/1933719114522518

Cited by 24 publications

(17 citation statements)

References 39 publications

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“…In addition to their use as research tools, false or misidentified cell lines such as HL-7702, TSCCA and BEL-7402 have been used in anti-cancer drug screening programs in respected centers in China. WISH, which has been reported as a HeLa contaminant for decades [37], was also on the panel of cell models for differentiation [38] in these institutions under its false identity-amnion cell line of human origin. Despite sporadic reports about cell line cross-contamination provided by cell repositories in China through systematic quality control check of their own cell lines, the tainted cell lines are still on sale for use.…”

Section: Discussionmentioning

confidence: 99%

Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines

et al. 2017

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In recent years, biological research involving human cell lines has been rapidly developing in China. However, some of the cell lines are not authenticated before use. Therefore, misidentified and/or cross-contaminated cell lines are unfortunately commonplace. In this study, we present a comprehensive investigation of cross-contamination and misidentification for a panel of 278 cell lines from 28 institutes in China by using short tandem repeat profiling method. By comparing the DNA profiles with the cell bank databases of ATCC and DSMZ, a total of 46.0% (128/278) cases with cross-contamination/misidentification were uncovered coming from 22 institutes. Notably, 73.2% (52 out of 71) of the cell lines established by the Chinese researchers were misidentified and accounted for 40.6% of total misidentification (52/128). Further, 67.3% (35/52) of the misidentified cell lines established in laboratories of China were HeLa cells or a possible hybrid of HeLa with another kind of cell line. Furthermore, the bile duct cancer cell line HCCC-9810 and degenerative lung cancer Calu-6 exhibited 88.9% match in the ATCC database (9-loci), indicating that they were from the same origin. However, when we used 21-loci to compare these two cell lines with the same algorithm, the percent match was only 48.2%, indicating that these two cell lines were different. The SNP profiles of HCCC-9810 and Calu-6 also revealed that they were different cell lines. 150 cell lines with unique profiles demonstrated a wide range of in vitro phenotypes. This panel of 150 genomically validated cancer cell lines represents a valuable resource for the cancer research community and will advance our understanding of the disease by providing a standard reference for cell lines that can be used for biological as well as preclinical studies.

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Section: Discussionmentioning

confidence: 99%

Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines

et al. 2017

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“…Previous studies have shown that soluble LDLR (sLDLR) secretion by cells can be induced by type I IFN and that sLDLR can inhibit VSV infection in WISH cells (this cell line was recently shown to be misidentified and identical to HeLa cells) (51)(52)(53). Although this mechanism cannot be responsible for the inefficient attachment of VSV to HPAF-II cells in our monolayer and suspension attachment assays (cells were washed before incubation with VSV), this sLDLR-mediated inhibition of VSV attachment could happen during multistep infection of cells, where HPAF-II cells show very strong resistance to VSV infection and replication.…”

Section: Vsv Attachment To Hpaf-ii Cells Is Impairedmentioning

confidence: 99%

“…First, to test whether sLDLR can inhibit VSV infectivity in PDAC cells, sLDLR and VSV or VSV alone was added to the cells, and the cells were incubated for 30 min at 37°C (the assay was conducted as described previously [51][52][53]). Cells were then washed to remove any unbound virus and overlaid with agar to prevent secondary infections.…”

Section: Vsv Attachment To Hpaf-ii Cells Is Impairedmentioning

confidence: 99%

Ruxolitinib and Polycation Combination Treatment Overcomes Multiple Mechanisms of Resistance of Pancreatic Cancer Cells to Oncolytic Vesicular Stomatitis Virus

Felt

Droby

Grdzelishvili

2017

J Virol

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Vesicular stomatitis virus (VSV) is a promising oncolytic virus (OV). Although VSV is effective against a majority of pancreatic ductal adenocarcinoma cell (PDAC) cell lines, some PDAC cell lines are highly resistant to VSV, and the mechanisms of resistance are still unclear. JAK1/2 inhibitors (such as ruxolitinib and JAK inhibitor I) strongly stimulate VSV replication and oncolysis in all resistant cell lines but only partially improve the susceptibility of resistant PDACs to VSV. VSV tumor tropism is generally dependent on the permissiveness of malignant cells to viral replication rather than on receptor specificity, with several ubiquitously expressed cell surface molecules playing a role in VSV attachment to host cells. However, as VSV attachment to PDAC cells has never been tested before, here we examined if it was possibly inhibited in resistant PDAC cells. Our data show a dramatically weaker attachment of VSV to HPAF-II cells, the most resistant human PDAC cell line. Although sequence analysis of low-density lipoprotein (LDL) receptor (LDLR) mRNA did not reveal any amino acid substitutions in this cell line, HPAF-II cells displayed the lowest level of LDLR expression and dramatically lower LDL uptake. Treatment of cells with various statins strongly increased LDLR expression levels but did not improve VSV attachment or LDL uptake in HPAF-II cells. However, LDLR-independent attachment of VSV to HPAF-II cells was dramatically improved by treating cells with Polybrene or DEAE-dextran. Moreover, combining VSV with ruxolitinib and Polybrene or DEAE-dextran successfully broke the resistance of HPAF-II cells to VSV by simultaneously improving VSV attachment and replication.IMPORTANCE Oncolytic virus (OV) therapy is an anticancer approach that uses viruses that selectively infect and kill cancer cells. This study focuses on oncolytic vesicular stomatitis virus (VSV) against pancreatic ductal adenocarcinoma (PDAC) cells. Although VSV is effective against most PDAC cells, some are highly resistant to VSV, and the mechanisms are still unclear. Here we examined if VSV attachment to cells was inhibited in resistant PDAC cells. Our data show very inefficient attachment of VSV to the most resistant human PDAC cell line, HPAF-II. However, VSV attachment to HPAF-II cells was dramatically improved by treating cells with polycations. Moreover, combining VSV with polycations and ruxolitinib (which inhibits antiviral signaling) successfully broke the resistance of HPAF-II cells to VSV by simultaneously improving VSV attachment and replication. We envision that this novel triple-combination approach could be used in the future to treat PDAC tumors that are highly resistant to OV therapy.KEYWORDS DEAE-dextran, combination treatment, oncolytic virus, pancreatic cancer, Polybrene, polycation, resistance, vesicular stomatitis virus, virus attachment, type I interferon, ruxolitinib

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“…Among these 70 misidentified human cell lines, 41 cell lines were used worldwide and 29 cell lines were established by Chinese scholars. 15 cell lines were in the Database of Cross-Contaminated or Misidentified Cell Lines of ICLAC (International Cell Line Authentication Committee), including the notable HeLa-replaced cell lines (ACC-2, ACC-M, KB and HEP-2) 8 – 11 , the glioma cell line SF767, which was substituted with the human cervical cancer cell line ME-180, and the nasopharyngeal carcinoma tumor lines CNE-1 and CNE-2, which are thought to be fusion cell lines between HeLa and another, unknown cell line 12 , 13 . Another 14 misidentified cell lines were reported in some papers 5 , 14 , 15 .…”

Section: Resultsmentioning

confidence: 99%

“…It was once the most widely used cell line due to its hardiness and rapid growth rate. However, it has been demonstrated that HeLa cells have contaminated many other cell lines; they have overgrown and completely replaced such original cell lines as WISH, KB, Hep-2, Chang Liver, INT407 and the adenoid cystic carcinoma cell lines ACC-2, ACC-3 and ACC-M 5 , 8 – 11 . From 1969 to 2004, 220 publications in the PubMed database were found to have used HeLa-contaminated cell lines 42 .…”

Section: Discussionmentioning

confidence: 99%

A Combination of Species Identification and STR Profiling Identifies Cross-contaminated Cells from 482 Human Tumor Cell Lines

Bian

Yang

Feng

et al. 2017

Sci Rep

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Human tumor cell lines are extremely important tools for cancer research, but a significant percentage is cross-contaminated with other cells. Short tandem repeat (STR) profiling is the prevailing standard for authenticating cell lines that originate from human tissues. Based on the analysis of 482 different human tumor cell lines used in China by STR, up to 96 cell lines were misidentified. More importantly, the study has found that STR profiling alone is insufficient to exclude inter-species cross-contamination of human cell lines. Among the 386 cell lines which had a correct STR profile, 3 of them were inter-species cross-contaminated. Careful microscopic examination may be helpful in some cases to detect changes in morphology but additional testing is needed. Additionally, species verification by PCR could easily identify the contaminants, even with a low percentage of contaminating cells. Combining STR profiling with species identification by PCR, more than 20.5% (99/482) of tumor cell lines were revealed as having been incorrectly identified, including intra-species (14.5%), inter-species (4.4%) cross-contamination and contaminating cell lines (1.7%). Therefore, quality control of cell lines is a systemic issue. Each cell line should undergo a full QA (Quality Assurance) assessment before it is used for research.

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Discovery of HeLa Cell Contamination in HES Cells: Call for Cell Line Authentication in Reproductive Biology Research

Cited by 24 publications

References 39 publications

Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines

Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines

Ruxolitinib and Polycation Combination Treatment Overcomes Multiple Mechanisms of Resistance of Pancreatic Cancer Cells to Oncolytic Vesicular Stomatitis Virus

A Combination of Species Identification and STR Profiling Identifies Cross-contaminated Cells from 482 Human Tumor Cell Lines

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