The developed model could lead to new discoveries in the study of differences between the sexes, and in the development of sex-adapted medicine. “This is a breakthrough in the field of gender medicine,” says Prof. Binyamin Raubinoff, director of the Institute for Genetic Therapy and a senior physician in the Department of Obstetrics and Gynecology B.
Published on: 1.12.22 13:57
“Male and female created them”: for the first time in the world – researchers from Hadassah Hospital succeeded in creating male and female cells with the same genetic load, from the same person. The developed model could lead to new discoveries in the study of differences between the sexes, and in the development of sex-adapted medicine.
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“In recent years, there is a growing understanding that the differences between the sexes affect health, and thereby the risk of getting sick and the course of the disease,” say Hadassah. “Women have a higher risk of getting sick, for example, from autoimmune diseases such as multiple sclerosis and rheumatoid arthritis, while men tend to have more significant morbidity when infected with corona and other infectious diseases. There are also differences in cardiac morbidity and various psychiatric disorders. In addition, there are differences between the sexes in the effectiveness and side effects of Medicines. Most of the medicines that have been taken off the shelves in recent years have been disqualified because they caused more severe side effects in women than in men. In light of this, the field of gender medicine has developed in the world of medicine, which researches and develops sex- and gender-adapted medicine.”
“Medical research, pharmaceutical companies and health authorities have been dealing with the differences between the sexes in recent years and the need to adjust treatments and determine drug doses according to the patient’s sex,” Hadassah says. “However, the research and development of the field has encountered difficulties. In nature, there are no genetically identical twins, one male and the other female. In the absence of a man and a woman with the same genetic load, when comparing the sexes today, a large number of women must be tested against men in order to overcome the natural genetic variation between people, which blurs the differences between male and female. In addition, when differences are found, it is impossible to know whether they arise from the sex chromosomes or from a different hormonal composition between males and females.”
“Headed by Prof. Binyamin Raubinoff, director of the Institute for Genetic Therapy and a senior physician in the Department of Obstetrics and Gynecology B, the biological sex is determined by the composition of the sex chromosomes of the fetus – the female cells contain two X chromosomes (XX), while the male has one X chromosome and a Y chromosome ( XY)”, further explained in Hadassah. “These differences cause the creation of unique reproductive organs for each sex, and the secretion of male and female hormones that also contribute to the differences between the sexes. The unique model of the male and female stem cells that have the same genetic load allows for a clear detection in the laboratory of differences between the sexes, in the absence of the masking that results from natural genetic variation between items, and bypasses the need for a comparative study of a large number of men and women. The stem cells can mature into every cell in the human body, therefore the model system developed will make it possible to study differences between the sexes in all types of cells, as well as to understand whether the cause of the difference is the composition of the sex chromosomes or the difference in the hormonal profile.” .
It should be noted that the research was carried out as part of the doctoral thesis of the physician-researcher Dr. Itai Waldhorn. “In order to develop the unique stem cells,” explains Dr. Waldhorn, “we used blood cells from a man with Klinefelter syndrome – a genetic syndrome in which the man has two X chromosomes and one Y chromosome (XXY), which occurs in 1 to 2 out of every 1000 males. The blood cell donor for our study was unique and one of the few Klinefelter loci in the world whose blood also contained small subpopulations of normal male (XY) and female (XX) cells. In the culture, the donor’s blood cells are induced into stem cells and we isolated stem cells that were genetically identical except for being male or female. The stem cells that were isolated have no hormonal expression, they can be sorted and matured into any cell type in the body and thus research the differences between males and females – in the absence as well as in the presence of sex hormones and distinguish between genetic and hormonal effects on differences between the sexes”.
“This is a breakthrough in the field of gender medicine,” explains Prof. Raubinoff. “The world of medical science today recognizes the great importance of the differences between women and men. The US National Institutes of Health (NIH) changed its policy in recent years, and now requires that all medical research funded by it be carried out equally for both sexes. The unique stem cell system we developed will lead to new discoveries about differences between the sexes, will be able to help compare the effectiveness and toxicity of drugs, and contribute to the development of better medicine adapted to men and women.”
It should be noted that the results of the study were published in the scientific journal of the International Society for Stem Cell Research Stem Cell Reports. Tikva Turetsky, Dr. Deborah Steiner, Dr. Yaniv Gil, and Dr. Michal Group – all from the Center for Stem Cell Research and the Institute for Genetic Therapy at Hadassah Hospital – also took part in the study. Dr. Hadar Binyamini from the Bioinformatics Unit also participated in the study. The Hebrew University.