Vermeulen Maxime, Giudice Maria-Grazia, Del Vento Federico, Wyns Christine
Gynecology-Andrology Research Unit, Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, Brussels, 1200, Belgium.
Department of Gynecology-Andrology, Cliniques Universitaires Saint-Luc, Brussels 1200, Belgium.
Stem Cells Cloning. 2019 Aug 5;12:27-48. doi: 10.2147/SCCAA.S178490. eCollection 2019.
While improvements made in the field of cancer therapy allow high survival rates, gonadotoxicity of chemo- and radiotherapy can lead to infertility in male and female pre- and postpubertal patients. Clinical options to preserve fertility before starting gonadotoxic therapies by cryopreserving sperm or oocytes for future use with assisted reproductive technology (ART) are now applied worldwide. Cryopreservation of pre- and postpubertal ovarian tissue containing primordial follicles, though still considered experimental, has already led to the birth of healthy babies after autotransplantation and is performed in an increasing number of centers. For prepubertal boys who do not produce gametes ready for fertilization, cryopreservation of immature testicular tissue (ITT) containing spermatogonial stem cells may be proposed as an experimental strategy with the aim of restoring fertility. Based on achievements in nonhuman primates, autotransplantation of ITT or testicular cell suspensions appears promising to restore fertility of young cancer survivors. So far, whether in two- or three-dimensional culture systems, in vitro maturation of immature male and female gonadal cells or tissue has not demonstrated a capacity to produce safe gametes for ART. Recently, primordial germ cells have been generated from embryonic and induced pluripotent stem cells, but further investigations regarding efficiency and safety are needed. Transplantation of mesenchymal stem cells to improve the vascularization of gonadal tissue grafts, increase the colonization of transplanted cells, and restore the damaged somatic compartment could overcome the current limitations encountered with transplantation.
虽然癌症治疗领域的进展使生存率提高,但化疗和放疗的性腺毒性可导致青春期前和青春期后的男性和女性患者不孕。通过冷冻保存精子或卵子以供未来辅助生殖技术(ART)使用,在开始性腺毒性治疗前保存生育能力的临床选择目前已在全球范围内应用。冷冻保存含有原始卵泡的青春期前和青春期后的卵巢组织,虽然仍被视为实验性方法,但自体移植后已成功诞下健康婴儿,且越来越多的中心开展此项操作。对于未产生可用于受精配子的青春期前男孩,可提出将含有精原干细胞的未成熟睾丸组织(ITT)冷冻保存作为一种实验性策略,旨在恢复生育能力。基于非人灵长类动物的研究成果,ITT或睾丸细胞悬液的自体移植似乎有望恢复年轻癌症幸存者的生育能力。到目前为止,无论是在二维还是三维培养系统中,未成熟的男性和女性性腺细胞或组织的体外成熟均未证明能够产生用于ART的安全配子。最近,已从胚胎干细胞和诱导多能干细胞中生成了原始生殖细胞,但在效率和安全性方面还需要进一步研究。间充质干细胞移植可改善性腺组织移植物的血管化、增加移植细胞的定植并恢复受损的体细胞区室,从而克服目前移植中遇到的限制。