A promising stem-cell-based approach for treating infertility has been successfully demonstrated in non-human primates, as reported in a study published by Cell Press in the November issue of the journal Cell Stem Cell. The preclinical study represents an important milestone for translating this strategy to the clinic, particularly for cancer survivors who have been rendered infertile by chemotherapy they received before reaching sexual maturity.
"This is the first study to demonstrate that transplanted spermatogonial stem cells can produce functional sperm in higher primates," says senior study author Kyle Orwig of the University of Pittsburgh and Magee-Womens Research Institute. "This is an important step toward human translation."
Cancer patients who undergo radiation therapy or chemotherapy often become infertile because these treatments damage dividing cells, including not only cancer cells but also spermatogonial stem cells (SSCs)--stem cells that develop into sperm. Prior to cancer therapy, adult men can cryopreserve their sperm and later use these cells to father children. But prepubertal boys don't have this option because they have not yet produced any mature sperm, so cancer treatments can leave them permanently infertile.
One promising strategy for these young patients is to preserve their SSCs before they undergo cancer therapy and later transplant these cells after they finish cancer treatment and reach sexual maturity. This approach has worked in a range of animal models, but past studies in large animals have primarily used radiation therapy to cause infertility, even though chemotherapy is also a common source of infertility in cancer patients.
In the new study, Orwig and his team cryopreserved SSCs from monkeys before treating them with a commonly used chemotherapy drug. After treatment, they injected the SSCs into the testes of these animals and found that the cells produced sperm in the majority of transplant recipients. Moreover, the SSC-derived sperm of one animal was capable of fertilizing egg cells and producing embryos that developed normally.
As noted in the accompanying In Translation article by Pierre Fouchet and colleagues, this work "constitutes a milestone in the field of reproduction, and generates hope for restoring fertility in survivors of childhood cancer."
Hermann et al.: "Spermatogonial stem cell transplantation into Rhesus testes regenerates spermatogenesis producing functional sperm."
Firlej et al.: "Stem Cell Therapy for Male Infertility Takes a Step Forward