The sex of a cell is determined by the presence of sex chromosomes: every cell can be categorized as either male or female. The significance of a cell’s sex is a concept that has been generally overlooked by the research community, but there is now a growing body of evidence that has some researchers examining important implications.”“Male cells have an X and a Y chromosome, while female cells have two X chromosomes,” said Cathy Fuller, Ph.D., associate professor in the Department of Cell, Developmental and Integrative Biology at UAB. “There is now good reason to consider that studies conducted in male cells will produce results different from those of identical studies using female cell lines. This could have a profound effect on fields such as personalized medicine.”
This month, Fuller, along with colleague Paul Insel, Ph.D., of the departments of Pharmacology and Medicine at the University of California-San Diego, published an editorial in the American Journal of Physiology-Cell Physiology called “I Don’t Know the Question, but Sex is Definitely the Answer!” The editorial comes on the heels of a 2012 decision by the American Physiology Society to require authors to report the sex of the cells lines, biological materials and animals used in their experiments.
Fuller and Insel looked at two articles published in AJP-Cell and one in Nature that laid out the reasons that the APS decision to disclose the sex of cell lines was essential. They wrote that the lessons learned from these articles suggest the APS policy could have an important effect on patient care.
“We have assumed that cells bearing an XY genotype behave the same as cells that are XX, but we don’t really know if that is correct,” said Fuller. “Do T-84 cells, derived from a male colon cancer patient, behave the same as Ht-29 colon cancer cells, derived from a female? And will a colon cancer drug tested in one cell line work in the same fashion in all patients?”
An additional complication, according to Fuller, is that many cell lines frequently used in research are old — some have been around for more than 50 years — and some supposedly male lines have lost the Y chromosome through the many repetitive cell culture cycles.
“As we move closer to the concept of personalized medicine, where drugs and therapies can be tailored for the individual patient, we will need a more complete understanding of the physiology of that patient down to the cellular level,” Fuller said. “A drug that was tested in a cell line without a Y chromosome might not work as well in a patient who does have Y chromosomes. This could help explain why certain drugs work better in some patients than in others.”
Fuller says investigators working on developing drugs such as small molecules and biologics will need to consider that sex differences may underlie differences in responsiveness of different cells used in high-throughput screens, as well as considering the sex of the patient group to whom the drugs are targeted. Sex differences will be particularly important in stem cell-based therapies, such that the sex of both the donor and the recipient should be considered.
She also suspects that other scientific journals will follow suit and require investigators to identify the sex of their cell lines. The good news is that the sex of many of the major cell lines currently in use is known and that information is available to researchers.