Human spermatogonial stem cells Growing hope for infertile male childhood cancer survivors

This dissertation focuses on male survivors of childhood cancer, who can become infertile due to the gonadotoxic effects of cancer treatments. Whereas adolescent and adult men can cryopreserve sperm prior to treatment as a method of fertility preservation, this option is not available to pre-pubertal patients due to the absence of spermatogenesis in the pre-pubertal testis. However, these patients are offered the option to collect and cryopreserve a testicular biopsy, harboring the spermatogonial stem cells (SSCs), which are present from birth onwards. In case of infertility in later life, the biopsy can be used to retrieve testicular cells including these SSCs, culture them to increase their numbers and autotransplant them into the healthy testis to restore spermatogenesis in the adult cancer survivor. However, this treatment is not clinically available yet, although good results have been obtained in animal models.
The research described in this work aimed to review knowledge gaps in the field; optimize the culture of SSCs to reduce the previously observed hindering overgrowth of somatic testicular cells; investigate ways to facilitate clinical implementation of the culture by using xenofree, scaled-up methods; and uncover perspectives of cancer survivors on the potential future use of this technique.
We found that growth of somatic cells could be limited by a combination of adaptations to the culture temperature, culture surface and medium components including growth factors. Additionally, patient perspectives revealed the necessity of a focus on reproductive autonomy during the course of their treatment, fertility consultations and future therapy.