Gynecology-Andrology Unit, Medical School, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, 1200 Brussels, Belgium.
Department of Gynecology-Andrology, Cliniques Universitaires Saint-Luc, 1200 Brussels, Belgium.
Int J Mol Sci. 2018 Jan 18;19(1):286. doi: 10.3390/ijms19010286.
Despite their important contribution to the cure of both oncological and benign diseases, gonadotoxic therapies present the risk of a severe impairment of fertility. Sperm cryopreservation is not an option to preserve prepubertal boys' reproductive potential, as their seminiferous tubules only contain spermatogonial stem cells (as diploid precursors of spermatozoa). Cryobanking of human immature testicular tissue (ITT) prior to gonadotoxic therapies is an accepted practice. Evaluation of cryopreserved ITT using xenotransplantation in nude mice showed the survival of a limited proportion of spermatogonia and their ability to proliferate and initiate differentiation. However, complete spermatogenesis could not be achieved in the mouse model. Loss of germ cells after ITT grafting points to the need to optimize the transplantation technique. Tissue engineering, a new branch of science that aims at improving cellular environment using scaffolds and molecules administration, might be an approach for further progress. In this review, after summarizing the lessons learned from human prepubertal testicular germ cells or tissue xenotransplantation experiments, we will focus on the benefits that might be gathered using bioengineering techniques to enhance transplantation outcomes by optimizing early tissue graft revascularization, protecting cells from toxic insults linked to ischemic injury and exploring strategies to promote cellular differentiation.
尽管性腺毒性疗法在治疗肿瘤和良性疾病方面做出了重要贡献,但它们也存在严重损害生育能力的风险。对于青春期前的男孩来说,精子冷冻保存并不是保留其生殖潜能的选择,因为他们的精小管仅包含精原干细胞(作为精子的二倍体前体)。在性腺毒性治疗之前冷冻保存人类未成熟睾丸组织(ITT)是一种被接受的做法。使用裸鼠异种移植评估冷冻保存的 ITT 显示,有限比例的精原干细胞得以存活,并具有增殖和启动分化的能力。然而,在小鼠模型中无法实现完全的精子发生。IT 移植后生殖细胞的丢失表明需要优化移植技术。组织工程是一门旨在使用支架和分子给药来改善细胞环境的新兴科学分支,可能是进一步发展的一种方法。在这篇综述中,在总结了人类青春期前睾丸生殖细胞或组织异种移植实验中获得的经验教训之后,我们将重点讨论使用生物工程技术可能带来的益处,通过优化早期组织移植物再血管化、保护细胞免受与缺血损伤相关的毒性侵袭以及探索促进细胞分化的策略来提高移植效果。