Spermatogonial stem cell preservation and restoration
PhD Student: Aude Braye
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. For almost 20 years, the research group BITE performed pioneering work to develop this strategy towards a clinical application.
For patients at high risk of losing their SSCs, the cryopreservation of SSCs is a valuable clinical tool to preserve their fertility. The research group BITE developed optimal protocols to cryopreserve either testicular cell suspensions or testicular tissue containing SSCs. These protocols are now being used in clinical fertility preservation programmes. The UZ Brussel started in 2002 to store testicular tissue of young boys who are at high risk of losing their spermatogonia.
In order to harvest their testicular tissue, these young boys need to undergo a testicular tissue biopsy. Although the biopsy procedure itself does not have a high complication rate, little is known about its effects on the long-term. BITE studies the effect of a testicular biopsy on the later pubertal development and fertility.
At adulthood, spermatogenesis could be restored by transplanting back the frozen-thawed SSCs into the cured patient. The technique of spermatogonial stem cell transplantation involves the injection of a testicular cell suspension containing SSCs into the seminiferous tubules. An alternative method is testicular tissue grafting. Testicular tissue fragments can be grafted into both ectopic and homotopic locations. The research group BITE was the first to show SSC differentiation in human tissue grafted into the mouse testis.
In vitro spermatogenesis
Principal Investigator: Prof. Dr. Ellen Goossens
Postdoctoral Researcher: Dr. Yoni Baert
Although donor gametes might offer a chance of starting a family for infertile patients, often the wish for genetic parenthood remains. Autotransplantation of spermatogonial stem cells (SSCs) could restore fertility, but only in certain cases. When transplantation is not applicable, in vitro spermatogenesis could result in patient-specific gametes. Research at BITE focusses on developing new culture systems for human in vitro spermatogenesis using state-of-the-art tissue engineering approaches such as organoid technology and 3D bioprinting. When SSCs can be retrieved from the patient, these primary cells can be used to differentiate towards fertilization-competent gametes. For patients lacking germ cells, patient-specific gametes can be derived by remodelling somatic cells into pluripotent stem cells followed by the differentiation towards germ cells.
Klinefelter Syndrome related infertility
PhD Student: Margo Willems
In 2009, a new research line considering fertility preservation in patients with Klinefelter Syndrome (KS) was started in the BITE lab. KS patients have one or more extra copies of the X-chromosome. These patients suffer from azoospermia due to a massive germ cell loss. However, in 50% of the patients, focal spermatogenesis is present which enables the testicular recovery of spermatozoa for Intracytoplasmic Sperm Injection (ICSI). In an attempt to preserve their fertility before the occurrence of germ cell loss, the recovery of spermatozoa at adolescent age or spermatogonial stem cells (SSCs) at prepubertal age was evaluated. Unfortunately, only limited numbers of SSCs were present in these biopsies. As germ cell loss occurs very early in life, early fertility preservation is not beneficial.
KS is highly underdiagnosed and most patients are only diagnosed when they contact a fertility center due to fertility problems. At the time of diagnosis, the testis is often highly fibrotic. The cause of this fibrotic process has not been identified. Current research in the BITE lab focuses on the occurrence of fibrosis in the KS testis. Next to this, we want to evaluate whether it is possible to predict the presence of spermatogenesis in the testis. At the moment, there are no clinical factors to predict successful recovery of testicular spermatozoa. We want to evaluate whether biomarkers in semen can predict ongoing spermatogenesis in a non-invasive manner.