Testicular tissue cryopreservation and spermatogonial stem cell transplantation to restore fertility: from bench to bedside

Abstract

Male infertility management has made significant progress during the past three decades, especially after the introduction of intracytoplasmic sperm injection in 1992. However, many boys and men still suffer from primary testicular failure due to acquired or genetic causes. New and novel treatments are needed to address these issues. Spermatogenesis originates from spermatogonial stem cells (SSCs) that reside in the testis. Many of these men lack SSCs or have lost SSCs over time as a result of specific medical conditions or toxic exposures. Loss of SSCs is critical in prepubertal boys who suffer from cancer and are going through gonadotoxic cancer treatments, as there is no option of sperm cryopresrvation due to sexual immaturity. The development of SSC transplantation in a mouse model to repopulate spermatozoa in depleted testes has opened new avenues of research in other animal models, including non-human primates. Recent advances in cryopreservation and in vitro propagation of human SSCs offer promise for human SSC autotransplantation in the near future. Ongoing research is focusing on safety and technical issues of human SSC autotransplantation. This is the time to counsel parents and boys at risk of infertility on the possibility of cryopreserving and banking a small amount of testis tissue for potential future use in SSC transplantation.

Optimizing methods for human testicular tissue cryopreservation and spermatogonial stem cell isolation

“…SSCs isolated by IP2 were successfully cultured in vitro over time (Figure A). Immunofluorescence imaging showed the expression of PLZF, a specific marker of undifferentiated human spermatogonia, as well as GFRα1 and SSEA4, as surface markers of undifferentiated spermatogonia, on day 10 of culture (Figure B). Immunostaining without primary antibodies was also used as the negative control (Supporting Information Figure ).…”

New promising strategies in oncofertility

“…The European Society of Human Reproduction (ESHRE) recommends that “in cases where no semen can be collected, the experimental techniques of cryopreservation of testicular tissue or suspensions of immature testicular cells including SSCs should be considered.” They further suggest that to “minimize trauma to the patient, the surgical recovery of testicular tissue should be combined with other interventions requiring anesthesia, such as bone marrow sampling or implantation of venous ports” [6, 50]. ASRM recommends that young boys and their parents receive counseling about the benefits of banking testes tissue for cryopreservation and later transplantation and that such offer be available only with an approved IRB protocol [51]. It should be noted that testicular tissue has a superior post-thaw viability rate (95%) as compared to SSC (66%) [52].…”

Spermatogonial Stem Cells: A Current Update in the Management of Azoospermic Infertile Men

“…However, male infertile patients caused by hypogonadism or undescended testis, the sperm are not successfully obtained. Thus, it is considered to perform SSCs (Goossens and Tournaye, 2014;Sadri-Ardekani et al, 2014). Recently, there are some possibility of SSCs utilization followed by ICSI in male infertility management such as artificial sperms formation by culture and autotransplantation of in vitro proliferated SSCs which under preclinical phase of development.…”