Although donor gametes might offer a chance of starting a family for infertile patients, the wish for genetic parenthood remains. Depending on the cause of infertility and the availability of cryostored testicular tissue of the patient, autotransplantation of spermatogonial stem cells (SSCs) could restore the fertility. However, when this is not applicable, in-vitro spermatogenesis (IVS) can still result in patient-specific gametes. As an adequate human in vitro spermatogenesis model has yet to be developed, research at BITE focusses on two approaches to obtain in-vitro derived sperm.
If SSCs can be retrieved from the patient, these primary cells can be used to differentiate towards fertilisation-competent gametes. However, only certain steps of human sperm production have been recapitulated in-vitro until now. Animal studies have underlined the importance of 3D spatial arrangements for in-vitro maturation. Therefore, to achieve human IVS, our group is developing new culture systems using state-of-the-art tissue engineering approaches, for instance testicular organoid technology. Organoid systems take advantage of the self-organizing capabilities of cells to create multi-cellular surrogates. The re-engineering of the human testicular microenvironment in a 3D organoid model might allow the differentiation of human SSCs in-vitro.
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. Life offspring in a mice model has been obtained using this technique. On the other hand, post-meiotic spermatid-like cells have been produced starting from human pluripotent stem cells but the efficiency remains very low. We aim to improve this process by taking the in-vivo signalling pathways of human spermatogenesis into account.