May 17, 2022 — University of Pennsylvania scientists who froze testicular tissue from rats more than 2 decades ago have discovered that 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 that tissue of this type has been frozen for such a long time and used to regenerate whole tissue,” said lead study author Eoin Whelan, PhD, of the Brinster Laboratory of Reproductive Physiology at the University of Pennsylvania School of Medicine. for Veterinary Medicine. “This has implications for a number of fields, including our focus, which is the restoration of fertility for children who have 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 obtain sperm, prepubertal boys, who do not yet produce sperm, have no options to preserve fertility.
The frozen samples from the study were spermatogenic stem cells, or SSCs — cells inside the testes that produce sperm later in life, Whelan says. Previous research has shown that 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, remained an open question — until now, that is.
From rats to mice
The rat cells, cryopreserved in 1996, were thawed and implanted into “naked” 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 with cells that had been frozen for only a few months. The long-frozen cells were able to grow and multiply in the mouse testes, generating the cells needed for sperm production, although 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, notes Whelan.
“That’s why we’re probably not talking about being able to restore natural fertility right now,” he says. “But keep in mind that all you need is one good sperm for conception. So even if the number is much lower, there is still a chance for successful conception.”
From mice to men
While banking testicular tissue is a promising way to protect fertility, it must first be tested in humans. Whelan thinks human clinical trials could begin within the next few years.
Meanwhile, clinics are offering to cryopreserve testicular tissue for prepubertal boys facing cancer treatment in the hope that technology will allow them to one day restore fertility, Whelan says. But the clock is ticking on those monsters.
“It’s not like we can keep waiting 20 years between trials,” says Whelan. “But it shows promise for those with childhood cancer, that they may have more fertility in the future than they thought.”
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