They point out the value of in situ screening of SSC viability, rather than relying on biochemical or cellular biomarkers, in identifying the potential of cryopreserved cells, which might not show the actual loss of stem cell potential over time. Second, while there currently are no protocols that can broaden human SSCs for reimplantation– a requirement for scientific advancement of this treatment– such procedures might require to consider time-dependent destruction of practicality, assuming human SSCs mimic those of rats.
Cross section of infertile mouse testis showing formerly frozen transplanted rat bacterium cells and sperm. Credit: Eoin Whelan, Whelan et al., 2022, PLOS Biology, CC-BY 4.0
Research study in mice holds ramifications for youth cancer survivors.
Male testis tissue that is cryopreserved can be reimplanted after more than 20 years and will go on to make practical sperm, according to a brand-new study in rodents. The research, by Eoin Whelan of the School of Veterinary Medicine, University of Pennsylvania and coworkers will be published publishing today (May 10th, 2022) in the open-access journal PLOS Biology. But the long delay includes a cost of minimized fertility compared to tissue that is just briefly frozen. The findings might have significant implications for the treatment of young male cancer patients, for whom chemotherapy might be preceded by the harvesting and freezing of testicular tissue for ultimate reimplantation.
Youth cancer survival rates have actually increased drastically in recent years, however a severe side result of treatment is reduced fertility later in life. A possible treatment would be to harvest, freeze, and reimplant testicular tissue, which contains stem cells, a procedure that has just recently been shown to restore fertility in a macaque design, a minimum of after short-term freezing.
But for pre-pubertal young boys with cancer, reimplantation might not be possible for a decade or more after collecting, raising the question of for how long frozen spermatogenic stem cells (SSCs) can stay feasible. To explore this question, the authors defrosted rat SSCs that had been cryopreserved in their laboratory for more than 23 years, and implanted them in so-called nude mice, which do not have an immune reaction that would otherwise decline the foreign tissue. They compared the ability of the long-frozen SSCs to produce feasible sperm to SSCs frozen for just a few months, and to freshly harvested SSCs, all from a single rat nest preserved over several years.
For pre-pubertal boys with cancer, reimplantation might not be possible for a decade or more after harvesting, raising the question of how long frozen spermatogenic stem cells (SSCs) can remain viable. They compared the ability of the long-frozen SSCs to produce practical sperm to SSCs frozen for only a couple of months, and to freshly gathered SSCs, all from a single rat colony maintained over several years.
The researchers discovered that the long-frozen SSCs had the ability to colonize the mouse testis and produce all of the essential cell types for effective sperm production, however not as robustly as SSCs from either of the more just recently gathered tissue samples. While the long-frozen SSCs had similar profiles of gene expression modifications compared to the other samples, they made less elongating spermatids, which go on to form swimming sperm.
They point out the value of in situ testing of SSC viability, rather than relying on biochemical or cellular biomarkers, in identifying the potential of cryopreserved cells, which may not show the actual loss of stem cell capacity over time. Second, while there presently are no procedures that can expand human SSCs for reimplantation– a requirement for medical development of this treatment– such protocols might need to consider time-dependent destruction of practicality, presuming human SSCs imitate those of rats.
Whelan adds, “Our research study showed that rat spermatogonial stem cells can be effectively frozen for over 20 years, transplanted into a sterile recipient animal and regrow the capability to produce sperm, albeit at a decreased rate. This might supply a method to recover the loss of fertility in prepubertal boys dealt with for cancer.”
Referral: “Reestablishment of spermatogenesis after more than twenty years of cryopreservation of rat spermatogonial stem cells exposes an essential impact in differentiation capacity” by Whelan EC, Yang F, Avarbock MR, Sullivan MC, Beiting DP, Brinster RL, 10 May 2022, PLOS Biology.DOI: 10.1371/ journal.pbio.3001618.
Financing: This work was moneyed by Robert J. Kleberg, Jr and Helen C. Kleberg Foundation (RLB). The funders had no function in study style, information collection and analysis, choice to release, or preparation of the manuscript.