Biological sex is a fundamental trait that influences development, reproduction, pathogenesis and medical treatment outcomes. Due to the masking effect of genetic differences and the hurdle to distinguish chromosomal versus hormonal effects, modeling sex differences is quite difficult.

A new study by the scientists of the Israeli Hadassah Medical Organization is a breakthrough in gender medicine. Scientists have created the world’s first human male and female cells with the same genetic code from the same person, differing only in sex chromosomes. This new and unique model could lead to discoveries in the research of sex differences and the development of gender medicine.

Stem cells have the remarkable potential to renew themselves. They can develop into many different cell types in the body. This breakthrough could provide a platform to establish gender differences in all cell types. It will also help understand if the cause of a difference is the composition of the sex chromosomes or the difference in the hormonal profile.

Scientists used the blood cells of a man with Klinefelter’s syndrome, a condition in which he has an extra X chromosome, to create the special stem cells (XXY). The genetic disorder occurs in 1 to 2 in 1,000 men.

The donor’s blood cells were converted into induced pluripotent stem cells and isolated stem cells, which were genetically identical except for their sex. Isolated stem cells can grow into any cell type, making them perfect for creating cellular models for investigating sex-related differences in all human cell types. Pluripotent stem cells can develop into different types of cells needed for therapeutic applications. In addition, the ability to examine sex differences in both the presence and absence of sex hormones and to distinguish between the effects of genetic and hormonal factors on sex differences is made possible by stem cells.

Physician researcher Ithai Waldhorn, MD, part of whose thesis the study was conducted, said: “The blood cell donor in our study was unique and one of the few Klinefelter patients in the world whose blood also had small subpopulations of normal male (XY) and female (XX) cells.”

Magazine reference:

  1. Ithai Waldhorn et al. Modeling sex differences in humans using isogenic induced pluripotent stem cells. Stem cell research. DOI: 10.1016/j.stemcr.2022.10.017