The Use of Cell Cultures in Biomedical Research: Successes and Avoiding the Pitfalls
A cell line is a permanently established cell culture generated from primary tissue that will proliferate indefinitely given appropriate fresh medium and space. Cell lines differ from primary cells in that they become immortalized and they have therefore assumed an important role in studying the physiological, pathophysiological, and differentiation processes of specific cells. It allows the examination of stepwise alterations in the structure, biology, and genetic makeup of the cell under controlled environments. Cell lines have been an indispensable tool in primary biomedical research leading to the development of vaccines, including the Polio vaccine, therapeutics for several diseases and cell culture methods have played a major part in the work of more than a third of the winners of the Nobel prize for medicine since 1953 and made gene therapy and stem cell research possible.
However, since the inception of modern cell culture methods in the 1950s a major problem has been the use of misidentified cell lines (e.g. HeLa) in preclinical biomedical research leading to the generation of questionable data. Despite the introduction of technologies to tackle this problem (cell line authentication technologies) this problem persists today. For example, a study by Christopher Korch, one of the founding members of the International Cell Line Authentication Committee (ICLAC), investigated the publication history of two cell lines. One was HEp-2, originally thought to be a laryngeal cancer cell line, and INT 407, originally thought to be derived from the intestine. However, both are HeLa contaminants, a cervical carcinoma cell line, and have been known to be so for more that 40 years. He found there had been over 7000 publications using these cell lines at an estimated research cost of hundreds of millions of pounds. Unfortunately, publications using these cell lines as models of laryngeal cancer and intestinal lines are still being published as recently as 2021. Authentication of cell lines is important in scientific research to ensure that researchers are not working with cells that are misidentified or cross-contaminated.
Authentication of cell lines is a fundamental part of good cell culture practice and is increasingly required to secure funding for research and for publication in scientific journals. The method of choice for the authentication of human cell lines is Short Tandem Repeat (STR profiling). This generates a unique DNA profile for human genomes (apart from identical twins) and has been adopted by the cell culture community. ECACC provides such a service with its AuthentiCellTM testing kit. The DNA profile generated can then be checked against a searchable STR profiling database such as ECACCs AuthenticellTM database.
Researchers need to ensure that prior to the commencement of any study involving the use of cell lines, the cell lines are authenticated to prevent the generation of potentially invalid and unpublishable data.
Written by Ed Burnett
October 2022