The site of sperm production, as shown in a coloured scanning electron micrograph image
STEVE GSCHMEISSNER / SCIENCE PHOTO LIBRARY
The first reliable way of isolating sperm stem cells from the testes and growing them outside the body could help infertile men have genetic children of their own.
A few teams have claimed to have isolated sperm stem cells before, but others have not been able to repeat the results. “The general feeling is that there is no reliable method,” says Miles Wilkinson at the University of California San Diego in the US.
His team has been studying the cells in the testes. By sequencing the RNA in single cells, they identified different cell types and found a marker protein on the surface of the stem cells that give rise to sperm, known as spermatogonial stem cells.
Using this marker, they isolated these cells from biopsies of testes. The resulting sets of cells do not consist solely of sperm stem cells but are far more highly enriched in them than anyone has achieved before.
The team found a way to keep these cells alive and growing for at least a month. The key is blocking something called the ATK pathway. In mice, blocking ATK makes stem cells differentiate, but Wilkinson found the opposite is true in humans.
“I think this is a really big step forward in our field,” says Ans van Pelt at the University of Amsterdam in the Netherlands, who was not involved in the study.
This could lead to treatments for some men who have mutations that stop these stem cells turning into sperm. For example, CRISPR gene editing has been used to correct these mutations in mouse sperm stem cells, which have restored fertility in mice once the stem cells were put back into the same animals. These stem cells have also as been used to produce sperm outside the body for IVF.
The biggest obstacle to doing this in people is the lack of a reliable way of isolating human sperm stem cells. Wilkinson says his team is focused on the basic science rather than the clinical applications but that it would be feasible to gene-edit the stem cells.
“That’s not something we’ve thought of doing, but you could,” he says. “As long as it’s for treating diseases and not for making people more intelligent or beautiful, I think it’s fine.”
“I’m not going to take a stand,” Wilkinson added later, referring to whether humans should be gene-edited. “I think it’s worth a debate.”
The work could also help some men who are infertile because of cancer treatments in childhood, before they began producing sperm that could be frozen. Sperm stem cells could be isolated using samples from testes taken before treatment, expanded in the lab and injected back into the testes to restore sperm production.
Van Pelt thinks labs would have to be able to grow sperm cells cells outside the body for at least two months to get enough to recolonise the testes, so we are not there yet. “But it’s a very good start,” she says.
Some men are infertile because of problems with the cells that surround the sperm-forming cells. So if ways can be found to turn sperm stem cells into sperm outside the body – as has already been done in mice – these men could father children via IVF.
Journal reference: PNAS, DOI: 10.1073/pnas.2000362117
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