The preservation and transplantation of spermatogonial stem cells (SSCs) is a potential strategy to circumvent sterility: frozen-thawed SSCs can be transplanted back into the cured patient to restore spermatogenesis. In the past 15 years, the research group BITE has performed pioneering work to develop this strategy towards a clinical application.
Cryopreservation of SSCs would be a valuable clinical tool for fertility preservation. In 1996, Avarbock and co-workers were the first to report on the successful cryopreservation of SSCs. Although frozen/thawed suspensions of murine spermatogonial cells were able to colonize recipient testes and initiate spermatogenesis, the search for an optimal freezing protocol is still ongoing.
A non-controlled freezing protocol has been described to yield the highest number of surviving cells after freeze-thawing. An alternative way of preserving stem cells is to freeze the whole testicular tissue.
We have ongoing research on the development of optimal protocols for cryopreserving either cell suspensions or prepubertal testicular tissue.
The technique of spermatogonial stem cell transplantation (SSCT) was introduced as a research model to study spermatogenesis. This model involves the introduction of a germ cell suspension from a fertile donor testis into the seminiferous tubules of an infertile recipient mouse. SSCs are able to relocate onto the basement membrane, proliferate and produce sperm cells. Healthy live offspring could be obtained from transplanted mice.
Our research focusses on the efficiency and safety of natural and assisted reproduction after SSCT in a mouse model. Research on the genetic and epigenetic aspects of SSCT has to be conducted prior to the clinical application of this technique.
With the approval of the ethical committee, we already started to store testicular tissue of male pre-pubertal patients who are at risk for getting sterile before the onset of spermatogenesis.
An alternative method for fertility preservation is testicular tissue grafting. Attempts have been made to graft immature and adult testicular tissue in both ectopic and homotopic locations. Pre-pubertal mouse tissue can be grafted successfully, with spermatogenesis in almost all the grafts, whereas adult grafts are generally lost because of sclerosis or atrophy. Our team was the first to show SSC differentiation in human tissue grafted in the mouse testis.
Because only 12% of the SSCs survives transplantation, the efficiency of reproduction after transplantation needs to be optimised. We want to investigate whether apoptotic mechanisms influence the efficiency of SSC colonisation after transplantation and whether the administration of anti-apoptotic means can increase the chance to father.