Researchers at Karolinska Institutet have demonstrated that early germ cells can be created from preserved testicular tissue of a boy undergoing cancer treatment. The study, published in the journal Human Reproduction Open, could ultimately contribute to new ways to protect and restore fertility after childhood cancer.
Some children undergoing intensive cancer treatment are at risk of becoming infertile because these treatments can also damage the cells that later form sperm. In the current study, the researchers investigated whether these sperm precursors could be recreated using other cells remaining in the testes.
The researchers used frozen testicular tissue from two prepubertal boys who had been treated for cancer and had few germ cells left. The remaining supporting cells were isolated from the tissue and reprogrammed into so-called induced pluripotent stem cells, cells that can grow into many different cell types. These were then directed to become early germ cells known as primordial germ cells.
Important proof of concept
Our results demonstrate that it is possible to generate induced pluripotent stem cells that generate early germ cells from frozen testicular tissue, even when the sample is severely affected by cancer treatment. ”
Tiago Macedo, first author, KI Women and Child Health Bureau Researcher
The researchers used a clinically compatible reprogramming protocol that facilitates future translational applications. The reprogrammed stem cells passed standard quality checks and were further induced into early germ cells with relatively high efficiency using two different methods.
This is a proof-of-concept study, demonstrating that the method and experimental pipeline are possible, but not ready for use in clinical practice. Further studies are required to ensure the robustness of the results, further mature the germ cells obtained here, and comprehensively validate their safety before clinical application.
Long-term vision for regenerative medicine
“In the short term, the results of this study will contribute to our understanding of how cancer treatments affect germ cells and the regenerative potential of preserved tissues, helping to develop protective strategies. In the long term, they may pave the way for new regenerative treatments to restore fertility in cancer survivors,” said first author João Pedro Alves López, a researcher in the department.
The study was carried out in collaboration with the NORDFERTIL consortium, Karolinska University Hospital, and other universities and hospitals in Sweden, Finland, and Belgium. This study was funded by the Birgitta and Karl-Axel Rydbeck Research Grant for Pediatric Research, the Swedish Research Council, the Swedish Childhood Cancer Foundation, and several international research programs, among others.
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Reference magazines:
Macedo, T. Others. (2026) Human iPSCs derived from cryopreserved testicular somatic cells enable germline regeneration in childhood cancer survivors. human reproductive open. DOI: 10.1093/hropen/hoag054. https://academic.oup.com/hropen/article/2026/3/hoag054/8701120
