Does co-transplantation of mesenchymal and spermatogonial stem cells improve reproductive efficiency and safety in mice?

ABSTRACT: BACKGROUND:Spermatogonial stem cell transplantation (SSCT) is a promising therapy in restoring the fertility of childhood cancer survivors. However, the low efficiency of SSCT is a significant concern. SSCT could be improved by co-transplanting transforming growth factor beta 1 (TGF?1)-induced mesenchymal stem cells (MSCs). In this study, we investigated the reproductive efficiency and safety of co-transplanting spermatogonial stem cells (SSCs) and TGF?1-induced MSCs. METHODS:A mouse model for long-term infertility was used to transplant SSCs (SSCT, n?=?10) and a combination of SSCs and TGF?1-treated MSCs (MSi-SSCT, n?=?10). Both transplanted groups and a fertile control group (n?=?7) were allowed to mate naturally to check the reproductive efficiency after transplantation. Furthermore, the testes from transplanted males and donor-derived male offspring were analyzed for the epigenetic markers DNA methyltransferase 3A (DNMT3A) and histone 4 lysine 5 acetylation (H4K5ac). RESULTS:The overall tubular fertility index (TFI) after SSCT (76?±?12) was similar to that after MSi-SSCT (73?±?14). However, the donor-derived TFI after MSi-SSCT (26?±?14) was higher compared to the one after SSCT (9?±?5; P?=?0.002), even after injecting half of the number of SSCs in MSi-SSCT. The litter sizes after SSCT (3.7?±?3.7) and MSi-SSCT (3.7?±?3.6) were similar but differed significantly with the control group (7.6?±?1.0; P?

SUBMITTER: Kadam P 

PROVIDER: S-EPMC6805426 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature