HeLa

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HeLa (cells)
HeLa-IV.jpg
Scanning electron micrograph of an apoptotic HeLa cell. Zeiss Merlin HR-SEM.
HeLa-I.jpg
Multiphoton fluorescence image of cultured HeLa cells with a fluorescent protein targeted to the Golgi apparatus (orange), microtubules (green) and counterstained for DNA (cyan). Nikon RTS2000MP custom laser scanning microscope.
 
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HeLa (cells)
HeLa-IV.jpg
Scanning electron micrograph of an apoptotic HeLa cell. Zeiss Merlin HR-SEM.
HeLa-I.jpg
Multiphoton fluorescence image of cultured HeLa cells with a fluorescent protein targeted to the Golgi apparatus (orange), microtubules (green) and counterstained for DNA (cyan). Nikon RTS2000MP custom laser scanning microscope.

A HeLa cell /ˈhlɑː/, also Hela or hela cell, is a cell type in an immortal cell line used in scientific research. It is the oldest and most commonly used human cell line.[1] The line was derived from cervical cancer cells taken on February 8, 1951,[2] from Henrietta Lacks, a patient who eventually died of her cancer on October 4, 1951. The cell line was found to be remarkably durable and prolific as illustrated by its contamination of many other cell lines used in research.[3][4]

George Otto Gey and Henrietta Lacks[edit]

The cells were propagated by George Otto Gey shortly before Lacks died of her cancer in 1951. This was the first human cell line to prove successful in vitro, which was a scientific achievement with profound future benefit to medical research. Gey freely donated these cells, along with the tools and processes his lab developed, to any scientist requesting them simply for the benefit of science. Neither Lacks nor her family gave Lacks's physician permission to harvest the cells, but, at that time, permission was neither required nor customarily sought.[5] The cells were later commercialized, although never patented in their original form. Then, as now, there was no requirement to inform a patient, or their relatives, about such matters because discarded material, or material obtained during surgery, diagnosis, or therapy, was the property of the physician and/or medical institution (this currently requires ethical approval and patient consent in the UK). This issue and Lacks's situation was brought up in the Supreme Court of California case of Moore v. Regents of the University of California. The court ruled that a person's discarded tissue and cells are not their property and can be commercialized.[6]

At first, the cell line was said to be named after a "Helen Lane" or "Helen Larson", in order to preserve Lacks's anonymity. Despite this attempt, her real name was used by the press within a few years of her death. These cells are treated as cancer cells, as they are descended from a biopsy taken from a visible lesion on the cervix as part of Lacks's diagnosis of cancer. A debate still continues on the classification of the cells.[citation needed]

HeLa cells, like other cell lines, are termed "immortal" in that they can divide an unlimited number of times in a laboratory cell culture plate as long as fundamental cell survival conditions are met (i.e., being maintained and sustained in a suitable environment). There are many strains of HeLa cells as they continue to mutate in cell cultures, but all HeLa cells are descended from the same tumor cells removed from Lacks. It has been estimated that the total number of HeLa cells that have been propagated in cell culture far exceeds the total number of cells that were in Henrietta Lacks's body.[7]

Use in research[edit]

HeLa cells were used by Jonas Salk to test the first polio vaccine in the 1950s. They were observed to be easily infected by poliomyelitis, causing infected cells to die.[8] This made HeLa cells highly desirable for polio vaccine testing since results could be easily obtained. A large volume of HeLa cells were needed for the testing of Salk’s polio vaccine, prompting the National Foundation for Infantile Paralysis (NFIP) to find a facility capable of mass-producing HeLa cells.[9] In the spring of 1953, a cell culture factory was established at Tuskegee University to supply Salk, as well as other labs, with HeLa cells.[10] Less than a year later, Salk’s vaccine was ready for human trials.[11]

HeLa cells were also the first human cells to be successfully cloned in 1955 by Theodore Puck and Philip I Marcus at the University of Colorado, Denver.[12] Since that time, HeLa cells have been used for "research into cancer, AIDS, the effects of radiation and toxic substances, gene mapping, and many other scientific pursuits".[13] According to author Rebecca Skloot, by 2009, "more than 60,000 scientific articles had been published about research done on HeLa, and that number was increasing steadily at a rate of more than 300 papers each month."[6]

HeLa cells have been used in testing how parvo virus infects cells of humans, HeLa, dogs, and cats.[14] These cells have also been used to study viruses such as the Oropouche virus (OROV). OROV causes the disruption of cells in cultured cells where cells begin to degenerate shortly after they are infected causing viral induction of apoptosis.[15] HeLa cells have been used in the study of the expression of the papillomavirus E2 and apoptosis.[16] HeLa cells have also been used to study canine distemper virus' ability to induce apoptosis in cancer cell lines.[17] This virus' ability to induce apoptosis could play an important role in developing treatments for tumor cells resistant to radiation and chemotherapy.[17] HeLa cells have also been used in a number of cancer studies including those involving sex steroid hormones such as Estradiol, estrogen, and estrogen receptors along with estrogen like compound such as Quercetin and its cancer reducing properties.[18] There have also been studies on HeLa cells, the effects of flavonoids and antioxidants with estradiol on cancer cell proliferation. HeLa cells were used to investigate the phytochemical compounds and the fundamental mechanism of the anticancer activity of the ethanolic extract of mango peel (EEMP). EEMP was found to contain various phenolic compounds and to activate death through apoptosis of human cervical malignant HeLa cells which suggests EEMP may help to prevent cervical cancer as well as other types of cancers.<[19]

In 2011, HeLa cells were used in tests of novel heptamethine dyes IR-808 and other analogs which are currently being explored for their unique uses in medical diagnostics, the development of theranostics, the individualized treatment of cancerous patients with the aid of PDT, co-administration with other drugs, and irradiation.[20][21] HeLa cells have been used in research involving fullerenes to induce apoptosis as a part of Photodynamic therapy as well as in in vitro cancer research using cell lines.[22] Further HeLa cells have also been used to define cancer markers in RNA, and have been used to establish an RNAi Based Identification System and Interference of Specific Cancer Cells.[23]

Telomerase[edit]

The HeLa cell line was derived for use in cancer research. These cells proliferate abnormally rapidly, even compared to other cancer cells. Like many other cancer cells,[24] HeLa cells have an active version of telomerase during cell division,[25] which prevents the incremental shortening of telomeres that is implicated in aging and eventual cell death. In this way the cells circumvent the Hayflick Limit, which is the limited number of cell divisions that most normal cells can later undergo before becoming senescent.

Chromosome number[edit]

Horizontal gene transfer from human papillomavirus 18 (HPV18) to human cervical cells created the HeLa genome which is different from Henrietta Lacks' genome in various ways, including its number of chromosomes. HeLa cells are rapidly dividing cancer cells, and the number of chromosomes varied during cancer formation and cell culture. The current estimate (excluding very tiny fragments) is a "hypertriploid chromosome number (3n+)" which means 76 to 80 total chromosomes (rather than the normal diploid number of 46) with 22–25 clonally abnormal chromosomes, known as HeLa signature chromosomes".,[26][26][27][28][29] The signature chromosomes can be derived from multiple original chromosomes making challenging summary counts based on original numbering. Researchers have also noted how stable these aberrant karyotypes can be.[26]

Human papillomaviruses (HPVs) are frequently integrated into the cellular DNA in cervical cancers. We mapped by FISH five HPV18 integration sites: three on normal chromosomes 8 at 8q24 and two on derivative chromosomes, der(5)t(5;22;8)(q11;q11q13;q24) and der(22)t(8;22)(q24;q13), which have chromosome 8q24 material. An 8q24 copy number increase was detected by CGH. Dual-color FISH with a c-MYC probe mapping to 8q24 revealed colocalization with HPV18 at all integration sites, indicating that dispersion and amplification of the c-MYC gene sequences occurred after and was most likely triggered by the viral insertion at a single integration site. Numerical and structural chromosomal aberrations identified by SKY, genomic imbalances detected by CGH, as well as FISH localization of HPV18 integration at the c-MYC locus in HeLa cells are common and representative for advanced stage cervical cell carcinomas. The HeLa genome has been remarkably stable after years of continuous cultivation; therefore, the genetic alterations detected may have been present in the primary tumor and reflect events that are relevant to the development of cervical cancer.[26]

Complete genome sequence[edit]

The complete genome of the HeLa cells was sequenced and published on 11 March 2013 [27][30] without the Lacks family’s knowledge.[31] After concerns were raised by the family, the authors voluntarily withheld access to the sequence data.[31] Another research paper about the HeLa sequencing project accepted for publication in March 2013 was also put on hold while the privacy concerns of the Lacks family were being addressed.[32] On 7 August 2013, NIH director Francis Collins announced a policy of controlled access to the cell line genome based on an agreement reached after three meetings with the Lacks family.[33] A data-access committee will review requests from researchers for accessing the genome sequence under the criteria that the study is for medical research and the users will abide by terms in the HeLa Genome Data Use Agreement, which includes that all NIH-funded researchers will deposit the data into a single database for future sharing. The committee consists of six members including representatives from the medical, scientific, and bioethics communities as well as two members of the Lacks family.[33] In an interview, Collins praised the Lacks family’s willingness to participate in this situation that was thrust upon them. He described the whole experience with them as ‘powerful’, saying that it brought together ‘science, scientific history and ethical concerns’ in a unique way.[34]

Contamination[edit]

Because of their adaptation to growth in tissue culture plates, HeLa cells are sometimes difficult to control. They have proven to be a persistent laboratory "weed" that contaminates other cell cultures in the same laboratory, interfering with biological research and forcing researchers to declare many results invalid. The degree of HeLa cell contamination among other cell types is unknown because few researchers test the identity or purity of already-established cell lines. It has been demonstrated that a substantial fraction of in vitro cell lines — estimates range from 10% to 20% — are contaminated with HeLa cells. Stanley Gartler in 1967 and Walter Nelson-Rees in 1975 were the first to publish on the contamination of various cell lines by HeLa.[35]

Science writer Michael Gold wrote about the HeLa cell contamination problem in his book A Conspiracy of Cells. He describes Nelson-Rees's identification of this pervasive worldwide problem — affecting even the laboratories of the best physicians, scientists, and researchers, including Jonas Salk — and many, possibly career-ending, efforts to address it. According to Gold, the HeLa contamination problem almost led to a Cold War incident: The USSR and the USA had begun to cooperate in the war on cancer launched by President Richard Nixon only to find that the exchanged cells were contaminated by HeLa. Gold contends that the HeLa problem was amplified by emotions, egos, and a reluctance to admit mistakes. Nelson-Rees explains:

It's all human – an unwillingness to throw away hours and hours of what was thought to be good research...worries about jeopardizing another grant that's being applied for, the hurrying to come out with a paper first. And it isn't limited to biology and cancer research. Scientists in many endeavors all make mistakes, and they all have the same problems.[36]

Rather than focus on how to resolve the problem of HeLa cell contamination, many scientists and science writers continue to document this problem as simply a contamination issue — caused not by human error or shortcomings but by the hardiness, proliferating, or overpowering nature of HeLa.[37] Recent data suggest that cross-contaminations are still a major ongoing problem with modern cell cultures.[3][38] Taken directly from the International Cell Line Authentication Committee (ICLAC) webpage:

Regrettably, cross-contamination and misidentification are still common within the research community. Many cell lines were cross-contaminated during establishment; this means that all work using those cell lines has incorrectly used the contaminant – which may come from a different species or a different tissue. ... A cell line is considered to be misidentified if it no longer corresponds to the individual from whom it was first established. Many cases of misidentification are caused by cross-contamination, where another, faster growing, cell line is introduced into that culture.[39]

Additional images[edit]

Helacyton gartleri: are HeLa cells human?[edit]

HeLa cells
Scientific classification
Kingdom:incertae sedis
Phylum:incertae sedis
Class:incertae sedis
Order:incertae sedis
Family:Helacytidae
Genus:Helacyton
Species:H. gartleri
Binomial name
Helacyton gartleri
Leigh Van Valen

Due to their ability to replicate indefinitely, and their non-human number of chromosomes, HeLa was described by Leigh Van Valen as an example of the contemporary creation of a new species, Helacyton gartleri. The species was named after Stanley M. Gartler, whom Van Valen credits with discovering "the remarkable success of this species."[40] His argument for speciation depends on these points:

This definition has not been followed by others in the scientific community, nor, indeed, has it been widely noted.[citation needed]

As well as proposing a new species for HeLa cells, Van Valen proposed in the same paper the new family Helacytidae and the genus Helacyton.[40] Recognition of Van Valen and Maiorana's names, however, renders Homo and Hominidae paraphyletic because Helacyton gartleri is most closely related to Homo sapiens.

However this proposal has not been taken seriously by other prominent evolutionary biologists or scientists in other disciplines. Van Valen’s argument of HeLa being a new species does not fulfill the criteria for an independent unicellular asexually reproducing species because of the notorious instability of the cancer karyotype and their lack of a strict ancestral-descendant lineage.[42][43] What is clear however is that they are not good representatives of human cells[citation needed] and if used as such should preferably be used alongside other human derived cell lines[citation needed], with a more normal karyotypes.

See also[edit]

References[edit]

  1. ^ Rahbari R, Sheahan T, Modes V, Collier P, Macfarlane C, Badge RM (2009). "A novel L1 retrotransposon marker for HeLa cell line identification". BioTechniques 46 (4): 277–84. doi:10.2144/000113089. PMC 2696096. PMID 19450234. 
  2. ^ Scherer WF, Syverton JT, Gey GO (1953). "Studies on the propagation in vitro of poliomyelitis viruses. IV. Viral multiplication in a stable strain of human malignant epithelial cells (strain HeLa) derived from an epidermoid carcinoma of the cervix". J. Exp. Med. 97 (5): 695–710. doi:10.1084/jem.97.5.695. PMC 2136303. PMID 13052828. 
  3. ^ a b Capes-Davis A, Theodosopoulos G, Atkin I, Drexler HG, Kohara A, MacLeod RA, Masters JR, Nakamura Y, Reid YA, Reddel RR, Freshney RI (2010). "Check your cultures! A list of cross-contaminated or misidentified cell lines". Int. J. Cancer 127 (1): 1–8. doi:10.1002/ijc.25242. PMID 20143388. 
  4. ^ Batts DW (2010-05-10). "Cancer cells killed Henrietta Lacks – then made her immortal". The Virginian-Pilot. pp. 1, 12–14. Retrieved 2012-03-17. ; Note: Some sources report her birthday as August 2, 1920, vice August 1, 1920.
  5. ^ Washington, Harriet "Henrietta Lacks: An Unsung Hero", Emerge Magazine, October 1994
  6. ^ a b Skloot, Rebecca (2010). The Immortal Life of Henrietta Lacks. New York: Crown/Random House. ISBN 978-1-4000-5217-2. 
  7. ^ Sharrer T (2006). ""HeLa" Herself". The Scientist 20 (7): 22. 
  8. ^ Scherer, W. F.; Syverton, JT; Gey, GO (1953). "Studies On The Propagation In Vitro Of Poliomyelitis Viruses: Iv. Viral Multiplication In A Stable Strain Of Human Malignant Epithelial Cells (Strain Hela) Derived From An Epidermoid Carcinoma Of The Cervix". Journal of Experimental Medicine 97 (5): 695–710. doi:10.1084/jem.97.5.695. PMC 2136303. PMID 13052828. 
  9. ^ Masters, John R. (2002). "TIMELINEHeLa cells 50 years on: the good, the bad and the ugly". Nature Reviews Cancer 2 (4): 315–319. doi:10.1038/nrc775. PMID 12001993. 
  10. ^ Turner, Timothy (2012). "Development of the Polio Vaccine: A Historical Perspective of Tuskegee University's Role in Mass Production and Distribution of HeLa Cells". Journal of Health Care for the Poor and Underserved 23 (4a): 5–10. doi:10.1353/hpu.2012.0151. 
  11. ^ Brownlee, K. A. (1955). "Statistics of the 1954 Polio Vaccine Trials*". Journal of the American Statistical Association 50 (272): 1005–1013. doi:10.1080/01621459.1955.10501286. 
  12. ^ Puck TT, Marcus PI (1955). "A Rapid Method for Viable Cell Titration and Clone Production with Hela Cells in Tissue Culture: The Use of X-Irradiated Cells to Supply Conditioning Factors". Proceedings of the National Academy of Sciences of the United States of America 41 (7): 432–7. PMC 528114. PMID 16589695. 
  13. ^ Smith, Van (2002-04-17). "The Life, Death, and Life After Death of Henrietta Lacks, Unwitting Heroine of Modern Medical Science.". Baltimore City Paper. Retrieved 2010-03-02. 
  14. ^ Parker, J; Murphy W, Wang D, O'Brien S, Parrish C (2001). "Canine and feline parvoviruses can use human or feline transferrin receptors to bind, enter, and infect cells". Journal of Virology 75 (8): 3896–3902. doi:10.1128/JVI.75.8.3896-3902.2001. PMC 114880. PMID 11264378. 
  15. ^ Acrani GO, Gomes R, Proença-Módena JL, da Silva AF, Carminati PO, Silva ML, Santos RI, Arruda E (2010). "Apoptosis induced by Oropouche virus infection in HeLa cells is dependent on virus protein expression". Virus Res. 149 (1): 56–63. doi:10.1016/j.virusres.2009.12.013. PMID 20080135. 
  16. ^ Hou, S.Y. Wu, S. Chiang, C. (2002). "Transcriptional activity among high and low risk human papillomavirus E2 proteins correlates with E2 DNA binding". The Journal of biological chemistry 277 (47): 45619–29. doi:10.1074/jbc.M206829200. PMID 12239214. 
  17. ^ a b Del Puerto HL, Martins AS, Milsted A, Souza-Fagundes EM, Braz GF, Hissa B, Andrade LO, Alves F, Rajão DS, Leite RC, Vasconcelos AC (2011). "Canine distemper virus induces apoptosis in cervical tumor derived cell lines". Virol. J. 8: 334. doi:10.1186/1743-422X-8-334. PMC 3141686. PMID 21718481. 
  18. ^ Bulzomi, Pamela (2012). "The pro-apoptotic effect of quercetin in cancer cell lines requires ERβ-dependent signals". Journal of cellular physiology 227 (5): 1891–8. doi:10.1002/jcp.22917. PMID 21732360. 
  19. ^ Hyeonji Kim, Hana Kim, Ashik Mosaddik, Rajendra Gyawali, Kwang Seok Ahn, Somi Kim Cho (2012). "Induction of apoptosis by ethanolic extract of mango peel and comparative analysis of the chemical consists of mango peel and flesh". Food Chemistry 133 (2): 416–422. doi:10.1016/j.foodchem.2012.01.053. 
  20. ^ Tan X, Luo S, Wang D, Su Y, Cheng T, Shi C (2011). "A NIR heptamethine Dye with intrinsic cancer targeting, imaging and photosynthesizing properties". Journal of Biomaterials China 33 (7): 2230–2239. doi:10.1016/j.biomaterials.2011.11.081. PMID 22182749. 
  21. ^ Pene, F.; Courtine, E.; Cariou, A. and Mira, J.P. (2009). "Toward theranostics". Crit Care Med 37: S50–S58<. doi:10.1097/CCM.0b013e3181921349. 
  22. ^ Briiuner., Thomas; Dieter F. Hulser (1990). "Tumor Cell Invasion and Gap Junctional Communication". Invasion Metastasis 10: :31–4. Retrieved 3 April 2012. 
  23. ^ Xie, Z, Wroblewska L, Prochazka L, Weiss R, Benenson Y. (2011). "Multi-Input RNAi-Based Logic Circuit for Identification of Specific Cancer Cells". Science 333 (6047): 1307–11. doi:10.1126/science.1205527. PMID 21885784. 
  24. ^ The Nobel Prize in Physiology or Medicine 2009 on nobelprize.org
  25. ^ Ivanković M, Cukusić A, Gotić I, Skrobot N, Matijasić M, Polancec D, Rubelj I (2007). "Telomerase activity in HeLa cervical carcinoma cell line proliferation". Biogerontology 8 (2): 163–72. doi:10.1007/s10522-006-9043-9. PMID 16955216. 
  26. ^ a b c d Macville M, Schröck E, Padilla-Nash H, Keck C, Ghadimi BM, Zimonjic D, Popescu N, Ried T (1999). "Comprehensive and definitive molecular cytogenetic characterization of HeLa cells by spectral karyotyping". Cancer Res. 59 (1): 141–50. PMID 9892199. 
  27. ^ a b Landry JJ, Pyl PT, Rausch T, Zichner T, Tekkedil MM, Stütz AM, Jauch A, Aiyar RS, Pau G, Delhomme N, Gagneur J, Korbel JO, Huber W, Steinmetz LM (2013). "The genomic and transcriptomic landscape of a HeLa cell line". G3 (Bethesda) 3 (8): 1213–24. doi:10.1534/g3.113.005777. PMC 3737162. PMID 23550136. 
  28. ^ Bottomley RH, Trainer AL, Griffin MJ. (1969). "Enzymatic and chromosomal characterization of HeLa variants". J Cell Biol. 41 (3): 806–15. doi:10.1083/jcb.41.3.806. PMC 2107821. PMID 5768876. 
  29. ^ Andrew Adey, Joshua N. Burton, Jacob O. Kitzman, Joseph B. Hiatt, Alexandra P. Lewis, Beth K. Martin, Ruolan Qiu, Choli Lee, Jay Shendure (8 August 2013). "The haplotype-resolved genome and epigenome of the aneuploid HeLa cancer cell line". Nature 500 (7461): 207–211. doi:10.1038/nature12064. PMC 3740412. PMID 23925245. 
  30. ^ Callaway, Ewen (15 March 2013). "Most popular human cell in science gets sequenced". Nature. doi:10.1038/nature.2013.12609. Retrieved 8 August 2013. 
  31. ^ a b Callaway, Ewen (27 March 2013). "HeLa publication brews bioethical storm". Nature. doi:10.1038/nature.2013.12689. Retrieved 8 August 2013. 
  32. ^ Callaway, Ewen (7 August 2013). "Deal done over HeLa cell line". Nature. doi:10.1038/500132a. Retrieved 8 August 2013. 
  33. ^ a b "NIH, Lacks family reach understanding to share genomic data of HeLa cells". The National Institutes of Health. 7 August 2013. Retrieved 8 August 2013. 
  34. ^ Callaway, Ewen (7 August 2013). "NIH director explains HeLa agreement". Nature. doi:10.1038/nature.2013.13521. 
  35. ^ Masters JR (2002). "HeLa cells 50 years on: the good, the bad and the ugly". Nat. Rev. Cancer 2 (4): 315–9. doi:10.1038/nrc775. PMID 12001993. 
  36. ^ Gold, Michael. A Conspiracy of Cells: One Woman's Immortal Legacy and the Medical Scandal It Caused. ISBN 978-0-88706-099-1. 
  37. ^ Wang H, Huang S, Shou J, Su EW, Onyia JE, Liao B, Li S (2006). "Comparative analysis and integrative classification of NCI60 cell lines and primary tumors using gene expression profiling data". BMC Genomics 7: 166. doi:10.1186/1471-2164-7-166. PMC 1525183. PMID 16817967. 
  38. ^ Nardone RM (2007). "Eradication of cross-contaminated cell lines: a call for action". Cell Biol. Toxicol. 23 (6): 367–72. doi:10.1007/s10565-007-9019-9. PMID 17522957. 
  39. ^ "ATCC® Standards Development Organization: The International Cell Line Authentication Committee (ICLAC)". Standards.atcc.org. Retrieved 2013-06-27. 
  40. ^ a b Van Valen LM, Maiorana VC (1991). "HeLa, a new microbial species". Evolutionary Theory & Review 10: 71–4. ISSN 1528-2619. 
  41. ^ Duesberg, P; Mandrioli, D; McCormack, A; Nicholson, JM (2011). "Is carcinogenesis a form of speciation?". Cell cycle (Georgetown, Tex.) 10 (13): 2100–14. PMID 21666415. 
  42. ^ Cohan, FM (2002). "What are bacterial species?". Annu. Rev. Microbiol 56: 457–487. doi:10.1146/annurev.micro.56.012302.160634. PMID 12142474. 
  43. ^ Queiroz, K (2005). "Ernst Mayr and the modern concept of species". Proc. Natl. Acad. Sci. 102 (Suppl 1): 6600–6607. doi:10.1073/pnas.0502030102. PMC 1131873. PMID 15851674. 

Further reading[edit]

External links[edit]