ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: Stem Cell Res Ther. 2018 Nov 21; 9 (1):317

Spermatogonial stem cell transplantation (SSCT) could become a fertility restoration tool for childhood cancer survivors. However, the colonization efficiency of transplanted spermatogonial stem cells (SSCs) in animal models is about 12%, and the effectiveness of this procedure needs to be improved before clinical implementation become feasible. Co-transplantation of mesenchymal stem cells (MSCs) increased colonization efficiency of SSCs, by restoring after gonadotoxic treatment the SSC specific tissue environment that provides a niche for the germ cells.

This is an experimental study on a mouse model of spermatogenesis damage. The model is similar to the damage induced by chemotherapies in cancer survivors because both spermatogonial stem cells and their surrounding mesenchymal niche were affected. The model was developed and used to transplant SSCs, MSCs, a combination of SSCs and MSCs, or a combination of SSCs and TGFß1-treated MSCs. A significant increase in testis size and testis-to-body ratio and resumption of spermatogenesis was found in all transplanted groups compared to controls. The best results were observed in mouse undergoing spermatogonial stem cells transplantation (SSCT) and TGFβ1-treated mesenchymal stem cells + SSCT (MSi-SSCT). The proportion of tubules containing spermatogenesis (TFI) was higher in the MSi-SSCT group, in which germline-specific gene expression was also confirmed. TGFβ1-treatment was also related to a higher localization of MSCs in the testis and less evident localization in different organs.

These findings suggest that TGFß1-treated mesenchymal stem cell may exert an anti-inflammatory effect resulting in a better engraftment of the transplanted germinal cells. More pre-clinical studies are needed to clarify the involved mechanisms and the reproductive safety has to be proven, but MSi-SSCT could represent an effective tool to improve colonization efficiency of transplanted spermatogonial stem cells.