American researchers have for the first time transplanted a patient's own immature germline stem cells, taken from him as a child before chemotherapy that left him sterile, into his testicle. It is not yet clear whether he has started producing sperm. A description of the technique is available on medRXiv.org, and the patient's story was told by the AP news agency.
Thanks to modern medicine, up to 85 percent of children with cancer survive to adulthood without relapses. At the same time, about one in three of them remains infertile as a result of chemotherapy - actively dividing stem cells of the germ line, which give rise to gametes (sperm and eggs), are sensitive to it. To enable cancer patients to have offspring in the future, cryopreservation of mature sperm or eggs is currently offered, but they are not produced before puberty.
Kyle Orwig’s lab at the University of Pittsburgh has been developing technology for cryopreserving and replanting germline stem cells (gametogonia) for years. After seeing positive results in monkeys, the researchers began preserving stem cells collected by needle biopsy from prepubertal children with cancer before chemotherapy. Since 2011, the lab has been storing purified cultures of these cells from about a thousand boys for clinical trials.
One of them was Jaiwen Hsu, who was diagnosed with bone cancer at the age of 11 and was prepared for chemotherapy. His parents contacted the University of Pittsburgh Medical Center and enrolled him in a stem cell cryopreservation program. More than 10 years later, he became the first patient with preserved cells to seek a transplant — a spermogram revealed predictable azoospermia (absence of live sperm in the ejaculate). He was not planning to start a family at the time, but wanted to know if the experiment would be successful.
In 2023, in a separate clinical trial, Orwig and colleagues performed an autologous transplant of a suspension of cells from a patient's testicle containing spermatogonia. To do this, the researchers used a technology they had developed and tested on animals, which involves inserting a needle under ultrasound guidance through the base of the scrotum into the rete testis (Hallerian network) - it is connected to all the seminiferous tubules where sperm are formed - and using this needle to precisely deliver stem cells.
The procedure went without complications, and the ultrasound showed that the testicular tissue had a normal structure. The patient's testosterone, follicle-stimulating hormone, and luteinizing hormone levels were normal, but inhibin B (a marker of spermatogenesis) was low. A spermogram a year after the transplant continued to show azoospermia. Oruig believes that it is too early to draw conclusions - in experiments on monkeys, spermatozoa after a similar procedure could only be obtained in small quantities by puncture, but they were successfully used for conception using the in vitro fertilization method. Xu, who is now 26, noted that regardless of the results, he is pleased with his participation in the development of the technology and is grateful to his parents who included him in this program.
In parallel with the preservation of germline stem cells, experiments are underway to cryopreserve whole fragments of testicular tissue. In January 2025, Ellen Goossens and her colleagues from the Free University of Brussels implanted such a fragment of a patient's own tissue for the first time. It was taken before chemotherapy at the age of 10 and stored for 16 years. It is also too early to evaluate the results of this experiment.
