Sperm stem cells restore male fertility

Men who lose the ability to produce sperm after chemotherapy might one day be able to regain their fertility. That's because, for the first time, infertility has been reversed in a male primate using an injection of stem cells.

Cancer drugs often work by destroying rapidly dividing cells, as these are a typical feature of cancer. Unfortunately, the drugs can also kill other rapidly dividing cells, including those that produce sperm. Some men choose to freeze sperm samples before therapy so they can use them for artificial insemination at a later date, but this is not an option for boys who have not yet reached puberty.

Kyle Orwig at the University of Pittsburgh School of Medicine in Pennsylvania may have a solution. He says that while boys don't make sperm cells, they do possess "spermatogonial" stem cells that will eventually produce them.

To see if these stem cells could be used to restore fertility, Orwig and his team took samples of the cells from the testes of prepubescent and adult male rhesus macaques, and froze them. The monkeys were then given chemotherapy agents known to shut down sperm production. A few months later, the researchers injected each monkey's own spermatogonial stem cells back into its testes.

Sperm production was re-established in nine of the 12 adult animals and started normally in three out of five prepubescent animals once they reached maturity. The resulting sperm were used to fertilise eggs and produce healthy embryos.

"I think this is the best option we have ever had," says Renee Reijo Pera, director of Stanford University's Center for Human Embryonic Stem Cell Research and Education, who wasn't involved in the study. "I know a lot of people have thought about doing this before but no has ever been able to successfully demonstrate this in a clinical setting with a species genetically very similar to us."

Orwig says there are some concerns that implanting stem cells could reintroduce cancer cells that may have been present in the original tissue. However, centres in the US and Europe are already banking testicular tissue for boys in the hope that new stem cell-based therapies will become available.

"In the most optimistic scenario our research suggests a man could have his own stem cells transplanted, giving him the opportunity to have children via natural intercourse," Orwig says. It's not yet ready for clinical translation, he says, "but it's an important step forward".

Journal reference: Cell Stem Cell, DOI: 10.1016/j.stem.2012.07.017

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