First-Ever Sperm Production Achieved After Re-Transplanting Childhood-Frozen Testicular Tissue

In a landmark achievement for oncofertility, a 27-year-old man has produced mature sperm following the re-transplantation of his own testicular tissue that had been cryopreserved before he underwent chemotherapy as a child. This represents the first time a transplant of frozen prepubertal testicular tissue has been demonstrated to restore sperm production in an adult patient.

The patient, who had the tissue sample frozen at age 10 before receiving high-dose chemotherapy and a bone marrow transplant for sickle cell disease (搜索)搜索该疾病, had four tissue fragments grafted back into his remaining testicle and four under the skin of the scrotum last year. After one year inside the body, the grafts were removed and analyzed. Two of the grafts from inside the testicle had produced mature sperm, which was subsequently collected and frozen.

"This is a huge finding," said Prof Ellen Goossens of the Vrije Universiteit Brussel查看公司主页, who led the trial. "Many more people will have hope that they can have biological children. It's great to see for the patients for whom we already have tissue banked."

A decades-long journey from bench to bedside

The Belgian clinic became the first worldwide to begin banking testicular tissue from prepubertal patients in 2002. The immature testes contain spermatogonial stem cells — the precursors of sperm — and Sertoli cells, essential nurse cells that support and nourish developing sperm. At that time, the field was in its infancy, with methods only just being developed in animal models.

"At that time this field was in its infancy," Goossens noted. "These methods were just being developed in animals. We told patients' families we couldn't guarantee that the fertility restoration would be successful."

The clinic's first wave of patients are now reaching their mid-20s, and some have reached the point of wanting to start a family. Because the tissue fragments are not directly connected to the sperm duct, researchers do not expect sperm cells to naturally find their way into the semen. The sperm that was isolated appeared morphologically normal, though Goossens cautioned: "We still have to see whether it's able to fertilise an egg."

The results are published in a preprint paper, which is yet to be peer reviewed. The first patient is now considering whether to undergo a second round of grafts to collect more sperm or to proceed with IVF in the near future.

Parallel advances in stem cell reprogramming

In complementary research, scientists at Karolinska Institutet查看公司主页 have demonstrated an alternative approach to fertility preservation. Published in the journal Human Reproduction Open, their proof-of-concept study shows that early germ cells can be generated from preserved testicular tissue of young boys facing cancer therapy — even when samples are severely affected by prior treatment.

The researchers used frozen testicular tissue from two prepubertal boys who had been treated for cancer and had very few remaining germ cells. Supporting cells were isolated and reprogrammed into induced pluripotent stem cells (iPSCs), which were then directed to become early germ cells known as primordial germ cells.

"Our results show that it is possible to generate induced pluripotent stem cells to produce early germ cells from frozen testicular tissue, even when these samples are severely affected by cancer treatment," said Tiago Macedo, first author and researcher at the Department of Women's and Children's Health, Karolinska Institutet查看公司主页.

The team employed a clinically compatible reprogramming protocol to facilitate future translational applications. The reprogrammed stem cells passed standard quality checks and were directed into early germ cells using two different methods with relatively high efficiency.

Clinical implications and the road ahead

"In the short term, the findings will contribute to understanding how cancer treatment affects germ cells and the regenerative potential of the preserved tissues, helping us to develop protective strategies," said leading author João Pedro Alves-Lopes, researcher at the same department. "In the long term, it could pave the way for new regenerative treatments to restore fertility in cancer survivors."

More than 3,000 patients worldwide already have testicular tissue banked. In the UK, it is estimated that approximately 200 patients each year would be likely to benefit from such approaches. Prof Rod Mitchell, a paediatric endocrinologist running a similar trial at the Centre for Reproductive Health at the University of Edinburgh查看公司主页, which began banking tissue in 2014 and has samples cryopreserved for more than 1,000 UK patients, expects his clinic to carry out the first transplants imminently.

"There is now proof of principle in humans that this approach is going to work, which is amazing," Mitchell said. "If you freeze tissue and keep cells alive, then they should have the potential. You're putting the tissue back into the perfect environment to stimulate it. Scientifically and biologically it makes sense. In reality, it's still amazing."

Mitchell added: "We're at a point where, internationally, we've been working on this for 15 years — in some cases more. It's all been about collecting tissue from the boys. Now it's coming to fruition. We're all super excited about it. One of the things we want to make sure is that people know about this. We know that we're not necessarily reaching all of them."

The Karolinska Institutet查看公司主页 study was conducted in collaboration with the NORDFERTIL consortium, Karolinska University Hospital, and other universities and hospitals in Sweden, Finland, and Belgium, with funding from the Birgitta and Carl-Axel Rydbeck's Research Grant for Paediatric Research, the Swedish Research Council, the Swedish Childhood Cancer Foundation, and several international research programs.