The debate over using primary cells versus cell lines continues to challenge researchers. It is widely understood that primary cells are a more biologically and physiologically relevant in vitro tool than cell lines for studying human and animal biology. However, for decades, cell lines have been used as a standard tool. Serially passaged, mischaracterized or contaminated cell lines have made their way into publications over the years. For example, a review about cell line quality summarized that 18–36% of cell lines are misidentified or cross-contaminated (Hughes P et al., 2007). Interestingly, a recent study indicates that oncology, by far, has the highest share of literature based on contaminated cell lines (Horbach et al., 2017). In the same article, the authors found that approximately 32,755 articles report on research with misidentified cells which, in turn, are cited by an estimated half a million other papers.
Even if a cell line is of the type that it is claimed to be, selective pressures and genetic drift over time can cause cell lines to exhibit reduced or altered functions. It is often the case that cell lines will mutate during serial passaging, and as a result show genotypic and phenotypic variation from the original donor. For example, Shaw et al demonstrated that the human embryonic kidney cell line HEK 293, derived by adenovirus transformation of primary cultures of HEK cells, bears a greater resemblance to neurons than to kidney cells1. Bioinformatic analysis of proteomic phenotypes revealed that the Hepa1–6 cell lines were deficient in mitochondria, reflecting rearrangement of metabolic pathways when compared to primary hepatocytes (Pan et al., 2009).
Check out further selected references discussing the concerns associated with the use of cell lines:
- The Cancer Conundrum – Increasing Clinical Success In Early Stage Drug Discovery
- Nature Journal – Announcement: Time to tackle cells’ mistaken identity
- Genetic and transcriptional evolution alters cancer cell line drug response
- Reading between the lines – new article references how genetic drifts in cell lines cause variances in experiments