# WI-38

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{{short description|Human cell line composed of fibroblasts}}
thumb|WI-38 cells (Left: in high density. Right: in low density)
'''WI-38''' is a diploid human cell line composed of [fibroblast](/source/fibroblast)s derived from lung tissue of a 3-month-gestation female fetus.<ref>{{cite web|title=WI-38 (ATCC® CCL-75™)|url=http://www.atcc.org/products/all/CCL-75.aspx}}</ref><ref name="Hayflick1961">{{cite journal | vauthors = Hayflick L, Moorhead PS | title = The serial cultivation of human diploid cell strains | journal = Experimental Cell Research | volume = 25 | issue = 3 | pages = 585–621 | date = December 1961 | pmid = 13905658 | doi = 10.1016/0014-4827(61)90192-6 }}</ref> The fetus came from a legal abortion performed in Sweden in 1962.<ref>{{Cite web |date=2020-11-04 |title=The controversial cells that saved 10 million lives |url=https://www.bbc.com/future/article/20201103-the-controversial-cells-that-saved-10-million-lives |access-date=2025-05-18 |website=www.bbc.com |language=en-GB}}</ref> The cell line was isolated by [Leonard Hayflick](/source/Leonard_Hayflick) the same year,<ref name=":0">{{Cite web| vauthors = Gorvett Z |title=The controversial cells that saved 10 million lives|url=https://www.bbc.com/future/article/20201103-the-controversial-cells-that-saved-10-million-lives|access-date=2020-12-09|website=www.bbc.com|language=en}}</ref><ref name=Hayflick1965>{{cite journal | vauthors = Hayflick L | title = The Limited in vitro Lifetime of Human Diploid Cell Strains | journal = Experimental Cell Research | volume = 37 | issue = 3 | pages = 614–36 | date = March 1965 | pmid = 14315085 | doi = 10.1016/0014-4827(65)90211-9 }}</ref> and has been used extensively in scientific research, with applications ranging from developing important theories in molecular biology and aging to the [production of most human virus vaccines](/source/Use_of_fetal_tissue_in_vaccine_development).<ref name="Fletcher1998">{{cite journal|vauthors=Fletcher MA, Hessel L, Plotkin SA|date=1998|title=Human diploid cell strains (HDCS) viral vaccines|journal=Developments in Biological Standardization|volume=93|pages=97–107|pmid=9737384}}</ref> The uses of this cell line in human virus vaccine production is estimated to have saved the lives of millions of people.<ref name=":0" /><ref name=Olshansky2017>{{cite journal | vauthors = Olshansky SJ, Hayflick L | title = The Role of the WI-38 Cell Strain in Saving Lives and Reducing Morbidity | journal = AIMS Public Health | volume = 4 | issue = 2 | pages = 127–138 | date = 2 March 2017 | pmid = 29546209 | pmc = 5689800 | doi = 10.3934/publichealth.2017.2.127 }}</ref><ref name="Nature">{{cite journal | vauthors = Wadman M | title = Medical research: cell division | journal = Nature | volume = 498 | issue = 7455 | pages = 422–6 | date = June 2013 | pmid = 23803825 | doi = 10.1038/498422a | doi-access =  | bibcode = 2013Natur.498..422W }}</ref>

==History==
The WI-38 cell line stemmed from earlier work by Hayflick growing human cell cultures.<ref name="Hayflick1961" />

In the early 1960s, Hayflick and his colleague Paul Moorhead at the [Wistar Institute](/source/Wistar_Institute) in [Philadelphia](/source/Philadelphia), [Pennsylvania](/source/Pennsylvania) discovered that when normal human cells were stored in a freezer, the cells remembered the doubling level at which they were stored and, when reconstituted, began to divide from that level to roughly 50 total doublings (for cells derived from fetal tissue). Hayflick determined that normal cells gradually experience signs of [senescence](/source/senescence) as they divide, first slowing before stopping division altogether.<ref name="Hayflick1961" /><ref name="Hayflick1965" /> This finding is the basis for the [Hayflick limit](/source/Hayflick_limit), which specifies the number of times a normal human cell population will divide before [cell division](/source/cell_division) stops.<ref name="Shay2000">{{cite journal | vauthors = Shay JW, Wright WE | title = Hayflick, his limit, and cellular ageing | journal = Nature Reviews. Molecular Cell Biology | volume = 1 | issue = 1 | pages = 72–6 | date = October 2000 | pmid = 11413492 | doi = 10.1038/35036093 | url = https://cogforlife.org/Hayflick.NatureNotImmortal.pdf | url-status = bot: unknown | s2cid = 6821048 | archive-url = https://web.archive.org/web/20100713062245/https://cogforlife.org/Hayflick.NatureNotImmortal.pdf | archive-date = 2010-07-13 }}</ref> Hayflick's discovery later contributed to the determination of the biological roles of telomeres.<ref name="Holliday2012">{{cite journal | vauthors = Holliday R | title = Telomeres and telomerase: the commitment theory of cellular ageing revisited | journal = Science Progress | volume = 95 | issue = Pt 2 | pages = 199–205 | year = 2012 | pmid = 22893980 | doi = 10.3184/003685012X13361526995348 | s2cid = 20557366 | doi-access = free | pmc = 10365536 }}</ref> Hayflick claimed that the finite capacity of normal human cells to replicate was an expression of aging or senescence at the cellular level.<ref name="Hayflick1961" /><ref name="Hayflick1965" /><ref name="Shay2000" />

During this period of research, Hayflick also discovered that if cells were properly stored in a freezer, cells would remain viable and that an enormous number of cells could be produced from a single starting culture. One of the cell strains that Hayflick isolated, which he named WI-38, was found to be free of contaminating viruses, unlike the primary monkey kidney cells then in use for virus vaccine production.<ref name="Hayflick1965" /> In addition, WI-38 cells could be frozen, then thawed and exhaustively tested. These advantages led to WI-38 quickly replacing primary monkey kidney cells for human virus vaccine production.<ref name="Olshansky2017" /><ref name="Nature" /><ref name="Hayflick2018" /> WI-38 has also been used for research on numerous aspects of normal human cell biology.<ref name="Nature" /><ref name="Shay2000" /><ref name=Hayflick2018>{{cite web | vauthors = Hayflick L | title = Errors in the "Vaccine Race" Book | url = http://www.aginginterventionfoundation.org/BookReview2.pdf | access-date = 2018-04-24 | archive-date = 2019-01-22 | archive-url = https://web.archive.org/web/20190122163226/http://www.aginginterventionfoundation.org/BookReview2.pdf | url-status = dead }}</ref>

==Applications==
WI-38 was invaluable to early researchers, especially those studying virology and immunology, since it was a readily available cell line of normal human tissue. Unlike the [HeLa cell line](/source/HeLa_cells), which were cancerous cells, WI-38 was a normal human cell population. Researchers in labs across the globe have since used WI-38 in their discoveries, most notably Hayflick in his development of human virus vaccines.<ref name="Olshansky2017" /> Infected WI-38 cells secrete the virus, and can be cultured in large volumes suitable for commercial production.<ref name="Hayflick1961" />

Virus vaccines produced in WI-38 have prevented disease or saved the lives of billions of people.<ref name="Olshansky2017" /><ref name="Nature" /> Vaccines produced in WI-38 include those made against [adenoviruses](/source/adenoviruses), [rubella](/source/Rubella_virus), [measles](/source/Measles_virus), [mumps](/source/Mumps_virus), [varicella zoster](/source/Varicella_zoster_virus), [poliovirus](/source/poliovirus), [hepatitis A](/source/Hepatitis_A_virus) and [rabies](/source/Rabies_virus).<ref name="Fletcher1998" /><ref name="Olshansky2017" /><ref name="Nature" /><ref name="Hayflick2018" />

== Genome sequence ==
The WI-38 cell line was one of the first cell lines whose ''diploid'' genome was sequenced.<ref name=":1">{{cite journal | vauthors = Soifer L, Fong NL, Yi N, Ireland AT, Lam I, Sooknah M, Paw JS, Peluso P, Concepcion GT, Rank D, Hastie AR, Jojic V, Ruby JG, Botstein D, Roy MA | display-authors = 6 | title = Fully Phased Sequence of a Diploid Human Genome Determined ''de Novo'' from the DNA of a Single Individual | journal = G3 | volume = 10 | issue = 9 | pages = 2911–2925 | date = September 2020 | pmid = 32631951 | pmc = 7466960 | doi = 10.1534/g3.119.400995 }}</ref> This is critical because most human genome sequences have not been resolved to [chromosome](/source/chromosome) level, that is, it remained largely unclear which genetic variant is on which of the two [chromatid](/source/chromatid)s. Besides being an important cell line for experimental studies (e.g. on aging), the WI-38 line is believed to have remained [diploid](/source/Ploidy) since it was originally established in 1961. Nearly 60 years later, [karyotyping](/source/Karyotype) by Soifer et al. (2020) showed that the WI-38 genome has not acquired major rearrangements such as [translocations](/source/Chromosomal_translocation). More importantly, the de novo phased assembly confirms that the genome has in fact remained diploid and retained its [heterozygosity](/source/Zygosity) throughout. It is therefore a good model for genome sequencing and serves as another reference genome.<ref name=":1" />

== See also ==
* [Use of fetal tissue in vaccine development](/source/Use_of_fetal_tissue_in_vaccine_development)
* [MRC-5](/source/MRC-5)

== References ==
{{reflist}}

== External links ==
* [Cellosaurus](/source/Cellosaurus) [http://www.cellosaurus.org/CVCL_0579 entry for WI-38]
* [https://www.nature.com/news/medical-research-cell-division-1.13273 Medical research: Cell division], by [Meredith Wadman](/source/Meredith_Wadman), 26. Jun 2013, Nature

Category:Human cell lines
Category:Cellular senescence
Category:1960s in biology
Category:1960s establishments in Pennsylvania
Category:History of medicine in the United States
Category:Vaccination
Category:Lung

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Adapted from the Wikipedia article [WI-38](https://en.wikipedia.org/wiki/WI-38) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/WI-38?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.