May 17, 2022 – University of Pennsylvania scientists who froze testicular tissue from rats over 2 decades ago have discovered the tissue is still viable, marking the latest step forward in keeping male cancer survivors fertile.
More than 23 years after the tissue was frozen, those rat cells were reimplanted and able to produce viable sperm, the researchers report in a new PLOS Biology paper.
“This is the first time tissue of this type has been frozen for such a long time and used to regenerate whole tissue,” says lead study author Eoin Whelan, PhD, of the Brinster Laboratory of Reproductive Physiology at the University of Pennsylvania School of Veterinary Medicine. “This has implications for a number of fields, including our focus, which is restoration of fertility for children who’ve undergone chemotherapy or ablative cell therapy.”
A side effect of such cancer treatments is lower fertility later in life, the researchers note. While adolescent boys can have sperm banked, prepubescent boys, who don’t yet produce sperm, have no options to preserve fertility.
The frozen samples from the study were spermatogenic stem cells, or SSCs – cells within the testes that produce sperm later in life, Whelan says. Previous research has shown these cells can remain viable after short-term freezing.
But whether the cells could last decades, for when a child is grown and ready to start a family, has remained an open question – until now, that is.
From Rats to Mice
Cryopreserved in 1996, the rat cells were thawed and implanted in “nude” mice, which lack an immune response that would otherwise reject the foreign tissue. Transplanting rat cells into mice allowed the researchers to distinguish between donor and host in their analysis, Whelan explains.
They compared the 23-year-old cells to cells frozen for only a few months. The long-frozen cells were able to grow and multiply in the mouse testes and generate the cells needed for sperm production, though not as strongly as the more recently harvested samples.
The older cells made fewer “elongating spermatids,” which form swimming sperm. And they produced only about a third of the sperm of the younger sample, Whelan notes.
“Because of that, we’re probably not talking about being able to recover natural fertility right now,” he says. “But keep in mind that all you need is one good sperm for fertilization. So even if the number is much lower, there’s still a chance for successful fertilization.”
From Mice to Men
While banking testicular tissue is a promising way to protect fertility, it must be tested in humans first. Whelan thinks human clinical trials could start within the next few years.
In the meantime, clinics are offering to cryopreserve testicular tissue for prepubescent boys facing cancer treatment in hopes that technology will allow them to restore fertility one day, Whelan says. But the clock is ticking on those samples.
“It’s not like we can keep waiting 20 years between trial periods,” Whelan says. “But this does show promise for those with childhood cancers, that they may have more fertility in the future than they thought.”