Jaiwen Hsu was an active 11-year-old when he developed pain in his left knee that forced him to sit out a few soccer games. What his parents thought was a sports injury turned out to be osteosarcoma, a type of bone cancer. He started chemotherapy, which doctors warned could result in infertility. Hsu hadn’t reached puberty yet, so sperm banking wasn’t an option. His parents enrolled him in a study that was collecting and storing immature testicular tissue, and the sperm-forming stem cells in them, from young patients with the goal of eventually giving them a way to have biological children. Now 26, Hsu and his doctors are waiting to see if an experimental transplant of these cells, extracted from a tissue sample taken back in 2011, will be able to restart sperm production. The procedure has been successful in mice and monkeys, but researchers say Hsu was the first person to undergo it in November 2023. The technique is detailed in a new paper that has yet to be peer-reviewed. “As an 11-year-old, I don’t think I could quite understand the severity of having a cancer diagnosis or comprehend the idea of starting a family down the road and how important that would be,” Hsu tells WIRED. In the early stages of his cancer treatment, Hsu and his family traveled from their home in Maryland to UPMC Children’s Hospital in Pittsburgh, where doctors collected a piece of testicular tissue containing the precious sperm stem cells. These stem cells are present even before puberty. During puberty, rising testosterone levels signal to these cells to develop into sperm, a process known as spermatogenesis. In November 2023, at age 24, Hsu was reunited with those cells. After undergoing anesthesia, he received an injection of them into one of his testes. The hope is that the cells engraft into the spaghetti-like tubules of the testis and develop into mature sperm. “If it works, those stem cells should regenerate spermatogenesis,” says Kyle Orwig, a professor of obstetrics, gynecology, and reproductive sciences at the University of Pittsburgh School of Medicine and the senior author on the new study. Even if it kickstarts sperm production, it might not be enough to come out in the ejaculate. “If there are, there definitely would not be enough sperm to restore natural fertility,” Orwig says. In animals, it’s possible to remove a larger piece of testicular tissue, which yields more stem cells, and more sperm. But in children undergoing cancer treatment, it’s important to minimize harm—and recovery time—so only a small amount of tissue is taken. That results in a relatively small number of stem cells. For that reason, Hsu will likely still need assistive reproductive technology if he wants to start a family. He’s not at that point yet, but said he chose to undergo the procedure now, in his mid-20s, because “it gives us a good time cushion to see if this works.” In the future, surgeons would likely need to cut into his testis and extract any sperm that might be there, which would then be used to fertilize an egg in a laboratory. Until Hsu is ready to have a child, researchers probably won’t know if the procedure worked. “What we expected out of this initial transplant was to demonstrate that the method was safe and that it was feasible,” Orwig says. Ultrasounds show that Hsu’s testicular tissue was unharmed by the procedure and his hormone levels are in the normal range. For now, his semen still lacks sperm. More transplants could happen soon. Orwig’s team has been banking testicular tissue from children since 2011, and now some of those patients are entering reproductive age. His group has received permission from the US Food and Drug Administration to do transplants of stem cells, as well as testicular tissue, as part of a clinical trial. Transplanting immature testicular tissue is an alternative approach that researchers are exploring. In that technique, a piece of preserved tissue is tucked under the skin of the scrotum. The hope is that the tissue will mature and eventually produce sperm. In monkeys, Orwig and his team transplanted testicular tissue, then removed that grafted tissue eight to 12 months later and extracted sperm from it. They used the sperm to fertilize eggs and transferred the resulting embryos into surrogate from female macaques, which resulted in a live birth. To retrieve the sperm, a sliver of tissue is cut away from the skin—a less invasive procedure than the stem cell transplant, which requires opening up the testis. When Orwig’s team first started collecting testicular tissue, he thought they would get more stem cells by isolating them from the tissue first and then freezing them. They did this with their first few patients, including Hsu. But later, they discovered they could get just as many stem cells or more from cryopreserving whole pieces of tissue, then later thawing them and extracting the cells. It meant that Hsu could only undergo a stem cell transplant, because just his cells were frozen. Other patients who froze whole pieces of tissue will have the option of trying either the stem cell or tissue transplant. In January, researchers at Vrije Universiteit Brussel and Brussels IVF in Belgium announced that they had performed the first testicular tissue transplant in a patient who underwent chemotherapy in childhood. The patient will be monitored for one year, with his semen being tested for the presence of sperm. After a year, doctors will remove some of the transplanted pieces of tissue to check for sperm. “For these patients who get life-saving cancer therapies, they are very often left with permanently impaired fertility as a result,” says Robert Brannigan, president-elect of the American Society for Reproductive Medicine and professor of urology at Northwestern University. “It’s hard to say which approach is going to be the one that is more effective, but I think both approaches really are worthy of further study.” A similar procedure, called ovarian tissue transplantation, is available for female cancer patients and has resulted in more than 200 live births worldwide. It’s more advanced than testicular freezing and transplantation because in adult men needing chemotherapy, there is usually the option of freezing sperm, whereas the equivalent practice in women—freezing eggs—can take two to three weeks, and patients may not have time to undergo it before starting chemotherapy. When egg freezing isn’t possible, a piece of tissue from the ovary can be collected and stored for later use. “It’s very nice to see that we are catching up a bit so that we can offer our young men the same sorts of opportunities we’re able to offer our young women,” says Jonathan Routh, a pediatric urologist at Duke Health. “Keeping kids alive is always goal number one, but allowing them to then live that life is really goal number two, and I think that’s where this study really will have an impact on the future.” Hsu realizes that the technology is still in its infancy, and it might not work for him. Even if he can’t have a biological child, he hopes these techniques will eventually open up options for other childhood cancer patients. “This is a practice that is just beginning,” he says. “The more support, the more research, and the more data we have, the better for people like me down the line.”