부산대학교 도서관

Background Spermatogonial stem cell transplantation (SSCT) could become a fertility restoration tool for childhood cancer survivors. However, since in mice, the colonization efficiency of transplanted spermatogonial stem cells (SSCs) is only 12%, the efficiency of the procedure needs to be improved before clinical implementation is possible. Co-transplantation of mesenchymal stem cells (MSCs) might increase colonization efficiency of SSCs by restoring the SSC niche after gonadotoxic treatment. Methods A mouse model for long-term infertility was developed and used to transplant SSCs (SSCT, n = 10), MSCs (MSCT, n = 10), a combination of SSCs and MSCs (MS-SSCT, n = 10), or a combination of SSCs and TGFss1-treated MSCs (MSi-SSCT, n = 10). Results The best model for transplantation was obtained after intraperitoneal injection of busulfan (40 mg/kg body weight) at 4 weeks followed by CdCl.sub.2 (2 mg/kg body weight) at 8 weeks of age and transplantation at 11 weeks of age. Three months after transplantation, spermatogenesis resumed with a significantly better tubular fertility index (TFI) in all transplanted groups compared to non-transplanted controls (P < 0.001). TFI after MSi-SSCT (83.3 [+ or -] 19.5%) was significantly higher compared to MS-SSCT (71.5 [+ or -] 21.7%, P = 0.036) but did not differ statistically compared to SSCT (78.2 [+ or -] 12.5%). In contrast, TFI after MSCT (50.2 [+ or -] 22.5%) was significantly lower compared to SSCT (P < 0.001). Interestingly, donor-derived TFI was found to be significantly improved after MSi-SSCT (18.8 [+ or -] 8.0%) compared to SSCT (1.9 [+ or -] 1.1%; P < 0.001), MSCT (0.0 [+ or -] 0.0%; P < 0.001), and MS-SSCT (3.4 [+ or -] 1.9%; P < 0.001). While analyses showed that both native and TGFss1-treated MSCs maintained characteristics of MSCs, the latter showed less migratory characteristics and was not detected in other organs. Conclusion Co-transplanting SSCs and TGFss1-treated MSCs significantly improves the recovery of endogenous SSCs and increases the homing efficiency of transplanted SSCs. This procedure could become an efficient method to treat infertility in a clinical setup, once the safety of the technique has been proven. Keywords: Fertility restoration, Infertility, Mesenchymal stem cells, Spermatogonial stem cells, Transplantation
Author(s): Prashant Kadam[sup.1] , Elissavet Ntemou[sup.1] , Yoni Baert[sup.1] , Sven Van Laere[sup.2] , Dorien Van Saen[sup.1] and Ellen Goossens[sup.1] Background Advanced cancer treatments have resulted in more than 80% [...]