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In world first, Israeli lab derives male and female stem cells from same person

Using cells identical in genetic composition, but not in gender, scientists hope to be better able to understand how drugs affect men and women differently

Nathan Jeffay is The Times of Israel's health and science correspondent

Illustrative image: artist's depiction of cells with X and Y chromosomes (frentusha via iStock by Getty Images)
Illustrative image: artist's depiction of cells with X and Y chromosomes (frentusha via iStock by Getty Images)

In a world first, Israeli scientists have derived male and female stem cells from the same person.

The researchers say they’ve successfully grown nervous system cells from the stem cells, with genetically identical male and female versions.

They note that the nervous system cells are a proof of concept, saying they are confident that any human cells can be obtained from the stem cells. The breakthrough was outlined in a peer-reviewed study, in which researchers around the world were offered the stem cells to explore their possibilities.

The Israeli scientists, from Hadassah Medical Center in Jerusalem, started with cells donated by a man who has both male and female cells due to a genetic syndrome.

The cells were in an international cell bank, and the technology to derive the stem cells isn’t new, but until now nobody took the initiative. “I really don’t know why it wasn’t done yet, because the benefits for medical science are very significant,” Prof. Benjamin Reubinoff told The Times of Israel.

Reubinoff, who led the research together with Dr. Ithai Waldhorn, said that the stem cells he derived could open up a new approach to investigating illnesses and medical treatments.

Prof. Benjamin Reubinof (courtesy of Hadassah Medical Center)

It’s known that men and women are often affected differently by medical conditions and by treatments. But when researchers try to document the differences in order to advance science, they often get stuck.

This is because, when people are recruited for studies, gender is only one factor that defines them. It’s often unclear whether people respond differently to an illness or treatment because of their gender, their genes, their health background, or a range of other factors.

“For the first time, we now have cells that are absolutely identical genetically, but in both male and female versions,” said Reubinoff. “This means that we can compare and contrast how they respond to the medication, or use them to model illness, without any of the ‘noise’ we’re used to.

“In other words, we’ll know in what ways, exactly, the cells act differently in male and female forms, instead of trying to derive this information from large studies. In studies, results might be due to gender, but equally might be due to genetic differences between participants.”

Reubinoff said that a potentially infinite supply of stem cells can be grown from those in his lab, and these could be used for huge numbers of experiments, in universities, hospitals and drug companies.

The research started when Waldhorn located rare cells from a man with Klinefelter syndrome. Normally, females have two X chromosomes, while males have one X and one Y chromosome. Klinefelter syndrome causes men to have two X chromosomes and one Y chromosome.

Dr. Ithai Waldhorn (courtesy of Hebrew University)

The man who donated the cells used by Reubinoff and Waldhorn is unusual among Klinefelter patients, in that his blood doesn’t only have the XXY cells that characterize the syndrome, but also small subpopulations of normal male (XY) and female (XX) cells. This is what enabled Reubinoff and Waldhorn to derive genetically identical stem cells in both male and female form.

Reubinoff hopes that other researchers will replicate their method with cells from some of the other few Klinefelter patients who have XX and XY cells.

He said that exploring the difference in how men and women respond to illnesses and drugs is essential. Women have a higher risk of developing, for example, autoimmune diseases such as multiple sclerosis and rheumatoid arthritis, while men are more likely to have more significant morbidity when infected with COVID-19 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 drugs.

“This is a breakthrough in the field of gender medicine,” said Reubinoff. “The world of medical science today recognizes the great importance of the differences between women and men.

“The National Institutes of Health in the US has changed its policy in recent years, now requiring that all medical research that it funds be conducted on both sexes equally. The unique stem cell system we have developed will lead to new discoveries about gender differences, and can help compare the efficacy and toxicity of drugs.”

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