Many
cell lines
An immortalised cell line is a population of cells from a multicellular organism which would normally not proliferate indefinitely but, due to mutation, have evaded normal cellular senescence and instead can keep undergoing division. The cell ...
that are widely used for
biomedical research
Medical research (or biomedical research), also known as experimental medicine, encompasses a wide array of research, extending from " basic research" (also called ''bench science'' or ''bench research''), – involving fundamental scienti ...
have been overgrown by other, more aggressive cells. For example, supposed thyroid lines were actually melanoma cells, supposed prostate tissue was actually bladder cancer, and supposed normal uterine cultures were actually breast cancer.
This is a list of cell lines that have been cross-contaminated and overgrown by other cells. Estimates based on screening of
leukemia
Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ...
-
lymphoma
Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enl ...
cell lines suggest that about 15% of these cell lines are not representative of what they are usually assumed to be. A project is currently underway to enumerate and rename contaminated cell lines to avoid errors in research caused by misattribution.
Contaminated cell lines have been extensively used in research without knowledge of their true character. For example, most if not all research on the
endothelium
The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the ve ...
ECV-304 or the
megakaryocyte
A megakaryocyte (''mega-'' + '' karyo-'' + '' -cyte'', "large-nucleus cell") is a large bone marrow cell with a lobated nucleus responsible for the production of blood thrombocytes (platelets), which are necessary for normal blood clotting. In h ...
DAMI cell lines has in reality been conducted on
bladder
The urinary bladder, or simply bladder, is a hollow organ in humans and other vertebrates that stores urine from the kidneys before disposal by urination. In humans the bladder is a distensible organ that sits on the pelvic floor. Urine enters ...
carcinoma
Carcinoma is a malignancy that develops from epithelial cells. Specifically, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that arises from cells originating in the endodermal, mesoderma ...
and
erythroleukemia
Acute erythrocyte leukemia is a rare form of acute myeloid leukemia (less than 5% of AML cases) where the myeloproliferation is of erythrocytic precursors. It is defined as type "M6" under the FAB classification.
Signs and symptoms
The most com ...
cells, respectively. Thus, all research on endothelium- or megakaryocyte-specific functions utilizing these cell lines has turned out to be misguided, serving more of a warning example.
There are two principal ways a cell line can become contaminated: cell cultures are often exchanged between research groups; if, during handling, a sample gets contaminated and then passed on, subsequent exchanges of cells will lead to the contaminating population being established, although parts of the supposed cell line are still genuine. More serious is contamination at the source: during establishment of the original cell line, some contaminating cells are accidentally introduced into the cultures, where they in time outgrow the desired cells. The initial testing, in this case, still suggested that the cell line is genuine and novel, but in reality, it has disappeared soon after being established and ''all'' samples of such cell lines are actually the contaminant cells. It requires lengthy research to determine the precise point where cell lines have become contaminated. A mix-up rated as contamination could in reality be a simple confusion of two cell lines, but usually contamination is assumed.
After a cell line has been discovered to be contaminated, they are usually never used again for research demanding the specific type of cell line they are assumed to be. Most contaminated cell lines are discarded, however sometimes contaminant cells have acquired novel characteristics (e.g., by
mutation
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, m ...
or viral
transfection
Transfection is the process of deliberately introducing naked or purified nucleic acids into eukaryotic cells. It may also refer to other methods and cell types, although other terms are often preferred: " transformation" is typically used to de ...
, for example the
HeLa
HeLa (; also Hela or hela) is an immortalized cell line used in scientific research. It is the oldest and most commonly used human cell line. The line is derived from cervical cancer cells taken on February 8, 1951, named after Henrietta ...
derivate Det98) and thus constitute a novel lineage after all, so are not thrown away. If a cell line is thought to be contaminated, it is usually tested for authenticity. The widespread contamination of HeLa cells was initially recognized by
Walter Nelson-Rees
Walter Nelson-Rees (11 January 1929 – 23 January 2009) was a cell culture worker and cytogeneticist who helped expose the problem of cross-contamination of cell lines. He used chromosome banding to show that many immortal cell lines, previousl ...
using simple
Giemsa
Giemsa stain (), named after German chemist and bacteriologist Gustav Giemsa, is a nucleic acid stain used in cytogenetics and for the histopathological diagnosis of malaria and other parasites.
Uses
It is specific for the phosphate groups of ...
stain
karyotyping
A karyotype is the general appearance of the complete set of metaphase chromosomes in the cells of a species or in an individual organism, mainly including their sizes, numbers, and shapes. Karyotyping is the process by which a karyotype is disce ...
under a
light microscope
The optical microscope, also referred to as a light microscope, is a type of microscope that commonly uses visible light and a system of lenses to generate magnified images of small objects. Optical microscopes are the oldest design of microsco ...
. This technique works well in recognizing HeLa because these cells have distinctive
chromosome
A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins ar ...
aberrations. Novel cell lines are proliferated and distributed and/or deposited at a safekeeping institution such as the
ATCC as soon as possible after establishment, to minimize the odds that the line becomes spoiled by contamination. It is considered
good practice
GxP is a general abbreviation for the "good practice" quality guidelines and regulations. The "x" stands for the various fields, including the pharmaceutical and food industries, for example good agricultural practice, or GAP.
A "c" or "C" is ...
to periodically check cell lines maintained under laboratory conditions (i.e., not placed in long-term storage) for contamination with HeLa or other common contaminants, to ensure that their quality and integrity is maintained.
Lists of contaminated cell lines
This list, containing 488 cell lines, was last updated on 1 December 2016.
Cellosaurus
Cellosaurus is an online knowledge base on cell lines, which attempts to document all cell lines used in biomedical research. It is provided by the Swiss Institute of Bioinformatics (SIB). It is an ELIXIR Core Data Resource as well as an I ...
also is maintaining a list of "problematic" cell lines.
[
The reference includes the list of linked pages in the search result.
] The list is dynamically generated from all cell lines in the database with a comment containing the dedicated words "Problematic cell line". , the list contains 757 entries.
If no species is given in the individual entries of the following tables, the table's species applies to both the assumed and the actual cell types.
Cell lines marked Virtual in the table below are known instances of contamination at the source; these cell lines became extinct or never existed. Cases where non-contaminated lines are ''known or strongly suspected'' to exist are marked Existent.
Contaminated human cell lines
Contaminated non-human cell lines
Notes
References
Bibliography
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External links
Cellosaurus list of problematics (contaminated/misidentified) cell lines">Cellosaurus">Cellosaurus
list of problematics (contaminated/misidentified) cell lines
{{DEFAULTSORT:Contaminated cell lines
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