Primary cell culture is the out-of-the-body cultivation of cells taken from a multicellular organism, as opposed to the culture of immortalized cell lines. Some countries, like the United Kingdom, have enacted laws acknowledging that primary cell cultures are more accurate representations of the body’s tissue than cell lines. Nevertheless, primary cells require sufficient substrate or nutrients and after a certain number of cell divisions, they develop a senescent phenotype that causes them to permanently stop dividing. These two motivations led to the creation of cell lines. Both naturally immortalized primary cells (such as HeLa cells) and artificially immortalized primary cells (such as HEK cells) may be sub-cultured indefinitely.
Primary cell cultures did not gain popularity until the 21st century because of the strict conditions under which they must be cultivated to ensure viability. In comparison to cell lines, these primary cells better mimic the cellular variability of tissues, maintain a more true transcriptome and proteomic profile (particularly when cultivated in 3D), and exhibit more realistic functional responses, including pharmacological reactions. In contrast, it is well-documented that immortalized cell lines experience genetic drift and acquire genetic abnormalities, and that they become homogeneous through the natural selection of certain subgroups. Oftentimes, cell lines have been incorrectly identified, contaminated with other cells, or infected with Mycoplasma, a microscopic intracellular bacterium that went undiscovered for decades.
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