Many cell lines that are widely used for biomedical research 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.[1] This is a list of cell lines that have been cross-contaminated and overgrown by other cells. Estimates based on screening of leukemia-lymphoma cell lines suggest that about 15% of these cell lines are not representative of what they are usually assumed to be.[2] A project is currently underway to enumerate and rename contaminated cell lines to avoid errors in research caused by misattribution.[3][4][a]
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 ECV-304 or the megakaryocyte DAMI cell lines has in reality been conducted on bladder carcinoma and erythroleukemia cells, respectively. Thus, all research on endothelium- or megakaryocyte-specific functions utilizing these cell lines has been misguided.
There are two principal ways in which a cell line can become contaminated: cell cultures are often exchanged between research groups; if, during handling, a sample is 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. In this case, the initial testing still suggests that the cell line is genuine and novel, but in reality, it disappeared soon after being established, and all samples of such cell lines are actually the contaminating cells. Lengthy research is required to determine the precise points where cell lines became contaminated. A mix-up rated as contamination could in reality be a simple confusion of two cell lines, but usually contamination is assumed.[citation needed]
After a cell line has been discovered to be contaminated, it is usually never used again for research demanding the specific type of cell line they were assumed to be. Most contaminated cell lines are discarded; however, sometimes contaminant cells have acquired novel characteristics (e.g., by mutation or viral transfection, for example the HeLa derivate Det98) and thus constitute a truly novel lineage, so they are not thrown away. If a cell line is thought to be contaminated, it is usually tested for authenticity.[b] The widespread contamination of HeLa cells was initially recognized by Walter Nelson-Rees using simple Giemsa stain karyotyping under a light microscope. This technique works well in recognizing HeLa because these cells have distinctive chromosome 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 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 are maintained.[citation needed]
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