Efficacy of Cellular Therapy for Azoospermia in Animal Models: A Systematic Review and Meta-Analysis

This study investigated the efficacy of stem cell transplantation for azoospermia, a major cause of male infertility. We conducted a systematic meta- analysis to assess the therapeutic effectiveness of stem cell transplant, using different transplant methods, injection sites, and stem cell types, and the reliability of this approach in different animal species. PubMed, the Cochrane Library, and Embase were searched for studies published from January 2006 to February 2022 that evaluated the use of stem cell transplant to treat azoospermia. We included 18 studies and conducted the analyses using Review Manager 5.2 software. Expression of the meiosis-related genes Vasa, Scp3, and Dazl and the average hematoxylin and eosin- positive staining area were improved after stem cell transplant. Subgroup analyses by mode of transplant showed higher expression of Scp3 and Dazl in the xenotransplant group. Although subgroup analyses by injection site showed that the seminiferous tubule group showed the most significant effect on Scp3 expression, spermatogenesis and repair of damaged testis were induced in the tunica albuginea group. The testicular torsion group also induced high levels of Scp3. Another subgroup analysis by stem cell type showed that umbilical cord mesenchymal stem cells promoted the highest expression of meiosis-related genes and successfully induced spermatogenesis and the repair of damaged testis. Urine-derived stem cells, spermatogonial stem cells, and amniotic fluid-derived stem cells showed significantly therapeutic effects; however, more studies are needed for definitive conclusions. Subgroup analyses by type of azoospermia animal model indicated that the use of stem cell transplant in rat or mouse models had an obvious therapeutic effect, but no significant therapeutic effect was seen in azoospermia hamsters. The meta-analysis confirmed that stem cell transplant can effectively treat azoospermia in animal models. Xenotransplant is shown to enhance the therapeutic effects of stem cell transplant on azoospermia.