ED27 trophoblast-like cells isolated from first-trimester chorionic villi are genetically identical to HeLa cells yet exhibit a distinct phenotype
Abstract
ED(27) trophoblast-like cells were prepared from human chorionic villus samples obtained at 9 weeks gestation and have been grown continuously in vitro without phenotypic drift for nearly a decade. These cells express many trophoblast markers, including cytokeratin, placental alkaline phosphatase (PLAP), secretion of 17beta-estradiol, and a microvillous apical surface. The ED(27) cell line is a useful model system for studies of placental cell biology and has been distributed to laboratories world-wide. However, experiments to investigate their relationship to primary villous cytotrophoblast have shown that these cells do not secrete detectable amounts of human chorionic gonadotropin in culture and, when digested with trypsin, disperse into individual cells. Furthermore, immunocytochemical studies demonstrated that, unlike villous cytotrophoblasts, ED(27) cells were immunoreactive with monoclonal antibodies recognizing some HLA Class I antigens. This was not HLA-G, however, as would be expected if these cells originated from extravillous cytotrophoblasts, but rather classical HLA-A, B which is thought not to be expressed by any trophoblast subpopulations. These inconsistencies prompted us to question the authenticity of the continuous cell line as it now exists. Genetic haplotype analysis using the polymerase chain reaction (PCR) revealed that ED(27) was genetically identically to the HeLa cell line. Inasmuch as HeLa cells have never been grown in the laboratory (DAK), the on…
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
STR-based detection found HeLa contamination in the human endometrial cell line HES.
“A striking example is the STR-based detection of HeLa contamination in the human endometrial cell line HES, highlighting the risk of secondary contamination [32,33].”
From The history, landscape, and outlook of human cell line authentication and security (2024) · cites this paper as [33]
Cites
Freshney, R. I. (2005) · Wiley eBooks · doi:10.1002/9780470649367 · Cited by 3,869 · see citing works
Kliman, H. J., Nestler, J. E., SERMASI, E., Sanger, J. M., & Strauss, J. F. (1986) · Endocrinology · doi:10.1210/endo-118-4-1567 · Cited by 1,572 · see citing works
Establishment and Characterization of First Trimester Human Trophoblast Cells with Extended Lifespan
Graham, C. H., Hawley, T. S., Hawley, R. G., MacDougall, J. R., Kerbel, R. S., Khoo, N. K. S., & Lala, P. K. (1993) · Experimental Cell Research · doi:10.1006/excr.1993.1139 · Cited by 1,056 · see citing works
Weiss, M. C., & Green, H. (1967) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.58.3.1104 · Cited by 514 · see citing works
Cross-contamination of cells in culture
Nelson-Rees, W. A., Daniels, D. W., & Flandermeyer, R. R. (1981) · Science · doi:10.1126/science.6451928 · Cited by 329 · see citing works
Nelson-Rees, W. A., & Flandermeyer, R. R. (1976) · Science · doi:10.1126/science.1246601 · Cited by 224 · see citing works
Banded Marker Chromosomes as Indicators of Intraspecies Cellular Contamination
Nelson-Rees, W. A., Flandermeyer, R. R., & Hawthorne, P. K. (1974) · Science · doi:10.1126/science.184.4141.1093 · Cited by 210 · see citing works
Cell Culture Models of Human Trophoblast II: Trophoblast Cell Lines—A Workshop Report
Shiverick, K. T., King, A., Frank, H., Whitley, G. S. J., Cartwright, J. E., & Schneider, H. (2001) · Placenta · doi:10.1053/plac.2001.0647 · Cited by 179 · see citing works
Douglas, G. C., & King, B. F. (1990) · Journal of Cell Science · doi:10.1242/jcs.96.1.131 · Cited by 178 · see citing works
Da, K., Pj, S., Pd, Z., Mb, L., & Sg, G. (1994) · PubMed · Cited by 160 · see citing works
The establishment of a line (WISH) of human amnion cells in continuous cultivation
Hayflick, L. (1961) · Experimental Cell Research · doi:10.1016/0014-4827(61)90059-3 · Cited by 156 · see citing works
Cell Culture Models of Trophoblast II: Trophoblast Cell Lines— A Workshop Report
King, A., Thomas, L., & Bischof, P. (2000) · Placenta · doi:10.1053/plac.1999.0526 · Cited by 135 · see citing works
Haigh, T., Chen, C.-P., Jones, C. J. P., & Aplin, J. (1999) · Placenta · doi:10.1053/plac.1999.0441 · Cited by 106 · see citing works
Yui, J., Garcia-Lloret, M., Brown, A. J., Berdan, R. C., Morrish, D. W., Wegmann, T. G., & Guilbert, L. J. (1994) · Placenta · doi:10.1016/0143-4004(94)90015-9 · Cited by 102 · see citing works
Examination of ATCC stocks for HeLa marker chromosomes in human cell lines
Lavappa, K. S., Macy, M. L., & Shannon, J. E. (1976) · Nature · doi:10.1038/259211a0 · Cited by 99 · see citing works
Survey of ATCC stocks of human cell lines for hela contamination
Lavappa, K. S. (1978) · In Vitro Cellular & Developmental Biology - Plant · doi:10.1007/bf02616110 · Cited by 94 · see citing works
Yagel, S., Casper, R. F., Powell, W., Parhar, R. S., & Lala, P. K. (1989) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(89)90314-1 · Cited by 89 · see citing works
Enzyme Polymorphisms as Genetic Signatures in Human Cell Cultures
O’Brien, S. J., Kleiner, G., Olson, R., & Shannon, J. E. (1977) · Science · doi:10.1126/science.841332 · Cited by 87 · see citing works
Establishment of clonal human placental cells synthesizing human choriogonadotropin.
CHOU, J. Y. (1978) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.75.4.1854 · Cited by 63 · see citing works
Kniss, D. A., Rovin, B. H., Fertel, R. H., & Zimmerman, P. D. (2001) · Placenta · doi:10.1053/plac.2000.0591 · Cited by 57 · see citing works
Self-citationExpression of Metalloproteinases and Their Inhibitors in Human Trophoblast Continuous Cell Lines
Morgan, M. P., Kniss, D. A., & McDonnell, S. (1998) · Experimental Cell Research · doi:10.1006/excr.1997.3929 · Cited by 55 · see citing works
Self-citationDiss, E., Gabbe, S. G., Moore, J. W., & Kniss, D. A. (1992) · American Journal of Obstetrics and Gynecology · doi:10.1016/s0002-9378(12)80036-6 · Cited by 54 · see citing works
Self-citationRong-Hao, L., Luo, S.-Y., & Zhuang, L. Z. (1996) · Human Reproduction · doi:10.1093/oxfordjournals.humrep.a019381 · Cited by 49 · see citing works
Imseis, H. M., Zimmerman, P. D., Samuels, P., & Kniss, D. A. (1997) · Placenta · doi:10.1016/0143-4004(77)90005-4 · Cited by 48 · see citing works
Self-citationImmortalization of virus-free human placental cells that express tissue- specific functions
Lei, K. J., Gluzman, Y., Pan, C. J., & CHOU, J. Y. (1992) · Molecular Endocrinology · doi:10.1210/me.6.5.703 · Cited by 43 · see citing works
O’Brien, S. J. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.141237598 · Cited by 43 · see citing works
Albert, J. L., Sundstrom, S. A., & LYTTLE, C. R. (1990) · PubMed · Cited by 43 · see citing works
Ma, T., Yang, S., & Kniss, D. A. (1999) · Tissue Engineering · doi:10.1089/ten.1999.5.91 · Cited by 38 · see citing works
Self-citationIs placental alkaline phosphatase (PLAP) a useful marker for seminoma?
Nielsen, O. S., Munro, A. J., Duncan, W. D., Sturgeon, J. F. G., Gospodarowicz, M. K., Jewett, M. A. S., Malkin, A., & Thomas, G. (1990) · European Journal of Cancer and Clinical Oncology · doi:10.1016/0277-5379(90)90049-y · Cited by 36 · see citing works
Differential gene expression in the amnion, chorion, and trophoblast of the human placenta
Plouzek, C. A., Leslie, K. K., Stephens, J. I., & CHOU, J. (1993) · Placenta · doi:10.1016/s0143-4004(05)80427-8 · Cited by 27 · see citing works
Thermotaxis of human trophoblastic cells
Higazi, A. A., Kniss, D. A., Manuppello, J. R., Barnathan, E., & Cines, D. B. (1996) · Placenta · doi:10.1016/s0143-4004(96)80019-1 · Cited by 19 · see citing works
Self-citationCharacterization of a TGFβ-responsive Human Trophoblast-derived Cell Line
Smith, A. N., Carter, Q. L., Kniss, D. A., & Brown, T. L. (2001) · Placenta · doi:10.1053/plac.2001.0653 · Cited by 19 · see citing works
Self-citationMonoclonal antibodies to cytotrophoblast and syncytiotrophoblast of human placenta.
Contractor, S. F., & Sooranna, S. R. (1986) · PubMed · Cited by 18 · see citing works
Toftager‐Larsen, K., Hørding, U., Dreisler, A., Daugaard, S., Lund, B., Bock, J. E., Lundvall, F., Frederiksen, K., & Nørgaard‐Pedersen, B. (2010) · Gynecologic and Obstetric Investigation · doi:10.1159/000294876 · Cited by 13 · see citing works
Flagged first, then by citations
1 of the 35 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
BMP4 initiates human embryonic stem cell differentiation to trophoblast
Xu, R., Chen, X., Li, D. S., Li, R., Addicks, G. C., Glennon, C., Zwaka, T. P., & Thomson, J. A. (2002) · Nature Biotechnology · doi:10.1038/nbt761 · Cited by 1,118 · see citing works
Sarker, S., Scholz‐Romero, K., Perez, A., Illanes, S. E., Mitchell, M. D., Rice, G. E., & Salomón, C. (2014) · Journal of Translational Medicine · doi:10.1186/1479-5876-12-204 · Cited by 411 · see citing works
Placental exosomes in normal and complicated pregnancy
Mitchell, M. D., Peiris, H. N., Kobayashi, M., Koh, Y. Q., Duncombe, G. J., Illanes, S. E., Rice, G. E., & Salomón, C. (2015) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2015.07.001 · Cited by 364 · see citing works
Placental Glucose Transfer and Fetal Growth
Baumann, M. U., Deborde, S., & Illsley, N. P. (2002) · Endocrine · doi:10.1385/endo:19:1:13 · Cited by 256 · see citing works
Korch, C. T., Spillman, M. A., Jackson, T. A., Jacobsen, B. M., Murphy, S. K., Lessey, B. A., Jordan, V. C., & Bradford, A. P. (2012) · Gynecologic Oncology · doi:10.1016/j.ygyno.2012.06.017 · Cited by 249 · see citing works
Rothenberg, S. P., Costa, M. P., Sequeira, J. M., Cracco, J. B., Roberts, J. L., Weedon, J., & Quadros, E. V. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa031145 · Cited by 241 · see citing works
Lala, P. K., & Chakraborty, C. (2003) · Placenta · doi:10.1016/s0143-4004(03)00063-8 · Cited by 188 · see citing works
Eradication of cross-contaminated cell lines: A call for action
Nardone, R. M. (2007) · Cell Biology and Toxicology · doi:10.1007/s10565-007-9019-9 · Cited by 124 · see citing works
Activation of NF-κB in Placentas of Women with Preeclampsia
Vaughan, J. E., & Walsh, S. W. (2012) · Hypertension in Pregnancy · doi:10.3109/10641955.2011.642436 · Cited by 123 · see citing works
Senescence of Primary Amniotic Cells via Oxidative DNA Damage
Menon, R., Boldogh, I. R., Urrabaz‐Garza, R., Polettini, J., Syed, T. A., Saade, G. R., Papaconstantinou, J., & Taylor, R. N. (2013) · PLoS ONE · doi:10.1371/journal.pone.0083416 · Cited by 112 · see citing works
Buhimschi, I. A., Jabr, M., Buhimschi, C. S., Petkova, A. P., Weiner, C. P., & Saed, G. M. (2004) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2004.03.081 · Cited by 111 · see citing works
Fuchs, R., & Ellinger, I. (2004) · Traffic · doi:10.1111/j.1600-0854.2004.00221.x · Cited by 101 · see citing works
Natural antimicrobial production by the amnion
Stock, S. J., KELLY, R. W., Riley, S. C., & Calder, A. A. (2007) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2006.10.908 · Cited by 80 · see citing works
Ackerman, W. E., Zhang, X. L., Rovin, B. H., & Kniss, D. A. (2005) · Biology of Reproduction · doi:10.1095/biolreprod.104.039032 · Cited by 78 · see citing works
Self-citationEndocrine cell lines from the placenta
Sullivan, M. H. F. (2004) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2003.03.001 · Cited by 74 · see citing works
OXIDATIVE STRESS REPRODUCES PLACENTAL ABNORMALITIES OF PREECLAMPSIA
Vaughan, J. E., & Walsh, S. W. (2002) · Hypertension in Pregnancy · doi:10.1081/prg-120015848 · Cited by 66 · see citing works
Lyall, F. (2003) · Microscopy Research and Technique · doi:10.1002/jemt.10278 · Cited by 57 · see citing works
Wang, S., Chen, J., Au, K. T., & Ross, M. G. (2003) · American Journal of Obstetrics and Gynecology · doi:10.1067/mob.2003.214 · Cited by 41 · see citing works
Kendal‐Wright, C. E., & Bryant-Greenwood, G. D. (2006) · Placenta · doi:10.1016/j.placenta.2006.03.011 · Cited by 38 · see citing works
Kniss, D. A., & Summerfield, T. L. (2014) · Reproductive Sciences · doi:10.1177/1933719114522518 · Cited by 33 · see citing works
Self-citationChaemsaithong, P., Luewan, S., Taweevisit, M., Chiangjong, W., Pongchaikul, P., Thorner, P. S., Tongsong, T., & Chutipongtanate, S. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24065658 · Cited by 23 · see citing works
Rashidi, H., Strohbuecker, S., Jackson, L. M., Kalra, S., Blake, A. J., France, L. L., Tufarelli, C., & Sottile, V. (2011) · Cells Tissues Organs · doi:10.1159/000329861 · Cited by 16 · see citing works
Quadros, E. V., Nakayama, Y., & Sequeira, J. M. (2013) · Journal of Cancer Therapy · doi:10.4236/jct.2013.46122 · Cited by 16 · see citing works
Hydrogen Peroxide Induced Apoptosis in Amnion-derived WISH Cells is not Inhibited by Vitamin C
Kumar, D., Lundgren, D. W., Moore, R. M., Silver, R. J., & Moore, J. J. (2003) · Placenta · doi:10.1016/j.placenta.2003.09.005 · Cited by 16 · see citing works
Establishment and characterization of a new human first trimester Trophoblast cell line, AL07
Liu, H., Wang, L., Wang, Y., Zhu, Q., Aldo, P. B., Ding, J., Mor, G., & Liao, A. (2020) · Placenta · doi:10.1016/j.placenta.2020.08.013 · Cited by 13 · see citing works
Serum amyloid A induces WISH cell apoptosis
JO, S., Yun, J., Jong-min, K. I. M., Lee, C., Baek, S., & Bae, Y. (2007) · Acta Pharmacologica Sinica · doi:10.1111/j.1745-7254.2006.00475.x · Cited by 12 · see citing works
Uchio, E., Inoue, H., Fuchigami, A., & Kadonosono, K. (2010) · Clinical and Experimental Ophthalmology · doi:10.1111/j.1442-9071.2010.02457.x · Cited by 12 · see citing works
Cytotoxic Effect of Advanced Glycation end Products
Boyanova, M., & Huppertz, B. (2009) · Biotechnology & Biotechnological Equipment · doi:10.1080/13102818.2009.10817615 · Cited by 10 · see citing works
Production of Human Trophoblast Cell Lines
Whitley, G. S. J. (2005) · Humana Press eBooks · doi:10.1385/1-59259-983-4:217 · Cited by 10 · see citing works
Effect of Nitric Oxide on Arachidonic Acid Release from Human Amnion-like WISH Cells
Biondi, C., Fiorini, S., Boarini, I., Barbin, L., Cervellati, F., Ferretti, M. E., & Vesce, F. (2002) · Placenta · doi:10.1053/plac.2002.0842 · Cited by 10 · see citing works
The history, landscape, and outlook of human cell line authentication and security
Harbut, E., Makris, Y., Pertsemlidis, A., & Bleris, L. (2024) · SLAS Discovery · doi:10.1016/j.slasd.2024.100194 · Cited by 8 · see citing works
Estrogen metabolites in the release of inflammatory mediators from human amnion-derived cells
Pavan, B., Paganetto, G., Dalpiaz, A., Biondi, C., & Lunghi, L. (2011) · Life Sciences · doi:10.1016/j.lfs.2011.01.018 · Cited by 7 · see citing works
Potential role of exosomes in reproductive medicine and pregnancy
Nair, S., & Salomón, C. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-816053-4.00016-x · Cited by 6 · see citing works
Wishing the WISH cells were pure
Ross, M. G., & Wang, S. (2003) · American Journal of Obstetrics and Gynecology · doi:10.1016/s0002-9378(03)00863-9 · Cited by 6 · see citing works
Histamine Stimulates Interleukin-6 Production through Histamine H1 Receptors in Human Amnion Cells
Morimitsu, A., Sumigama, S., Kotani, T., Mano, Y., Suzuki, K., 荒木, 雅., Yamamoto, E., Hayakawa, H., Okada, M., Itakura, A., et al. (2009) · Gynecologic and Obstetric Investigation · doi:10.1159/000257663 · Cited by 4 · see citing works
Targeted Mass Spectrometry-Based Proteomics Method to Quantify Placental Extracellular Vesicles
Lai, A., Palma, C., Salas-Burgos, A., Carrión, F., & Salomón, C. (2022) · Methods in molecular biology · doi:10.1007/978-1-0716-2341-1_6 · Cited by 1 · see citing works
Johnson, M. (2012) · Materials and Methods · doi:10.13070/mm.en.2.145
(2010) · Wiley eBooks · doi:10.1002/9780470649367.refs
Millar, L. K. (2003) · American Journal of Obstetrics and Gynecology · doi:10.1016/s0002-9378(03)00864-0
- Authors
- Kniss, D. A., Xie, Y., Li, Y., Kumar, S., Linton, E. A., Cohen, P., Fan-Havard, P., Redman, C. W. G., & Sargent, I. L.
- Affiliations
- The Ohio State University (US)
- Venue
- Placenta
- Publisher
- Elsevier BV
- Published
- 2002-01
- Volume
- 23
- Issue
- 1
- Pages
- 32-43
- ISSN
- 0143-4004 (ISSN-L)
- OpenAlex
- W2013571179
- Cited by
- 39
- References
- 35
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 1 · 2020: 1 · 2019: 1 · 2015: 1 · 2014: 2 · 2013: 2 · 2012: 3
- FWCI
- 1.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Placenta (publishedVersion)
- PubMed (publishedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- Funders
- Ohio State University
- National Institutes of Health (5r01hd035881-04)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01 HD-35881)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Gestational Trophoblastic Disease Studies
- Keywords
- trophoblast-like cells, chorionic villi, first trimester, HLA class I antigens, placental alkaline phosphatase, estrogen secretion, villous cytotrophoblast, cell line quality control
- MeSH terms
- Adult, Cell Line, Transformed, Chorionic Villi, DNA, Equipment Contamination, Female, Flow Cytometry, Haplotypes, HeLa Cells, Humans, Immunohistochemistry, Phenotype, Pregnancy, Pregnancy Trimester, First, Trophoblasts, Histocompatibility Antigens Class I, Biomarkers, Polymerase Chain Reaction, Culture Techniques
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
