围绕体外精子发生（IVS）的最新进展显示出在未来针对患有非梗阻性无精子症（NOA）的男性生育治疗中创建再生医学新范例的潜力。男性不育症是一种常见疾病，影响约 15% 的夫妇，其中 15% 的不育男性存在无精症（Cocuzza 等人，2013 年；Esteves 等人，2011a）。 NOA 患者的治疗主要限于手术取精联合体外受精胞浆内单精子注射 (IVF-ICSI)；然而，这些患者中只有一半的精子取出是成功的，活产率通常在 10% 到 25% 之间（Aljubran 等人，2022）。因此，该患者群体非常需要再生疗法。 IVS 被认为是进一步了解精子发生的分子和细胞过程的模型，也是一种潜在的再生治疗方法。虽然之前的研究已经尝试使用人类睾丸细胞进行二维细胞培养，但缺乏适当的空间排列限制了生殖细胞的分化和成熟，给临床应用带来了挑战。最近的研究表明，3D 技术可能对 IVS 具有优势，因为它可以模仿人类睾丸组织的天然细胞结构以及直接或间接的细胞间通讯。 3D 器官型培养物、支架、类器官、微流体、芯片睾丸和生物打印技术都显示出对再生治疗策略技术做出贡献的潜力，包括体外受精 (IVF)。尽管前景广阔，但仍需要进一步的工作来开发为人类成功、可复制且安全的 IVS 技术。 IVS 开发中组织工程、分子生物学和生殖医学之间的交叉允许多学科参与，克服挑战以实现再生疗法作为可行的选择。版权所有 © 2024。由 Elsevier Ltd 出版。

Recent advances surrounding in vitro spermatogenesis (IVS) have shown potential in creating a new paradigm of regenerative medicine in the future of fertility treatments for males experiencing non-obstructive azoospermia (NOA). Male infertility is a common condition affecting approximately 15% of couples, with azoospermia being present in 15% of infertile males (Cocuzza et al., 2013; Esteves et al., 2011a). Treatment for patients with NOA has primarily been limited to surgical sperm retrieval combined with in vitro fertilization intracytoplasmic sperm injection (IVF-ICSI); however, sperm retrieval is successful in only half of these patients, and live birth rates typically range between 10 and 25% (Aljubran et al., 2022). Therefore, a significant need exists for regenerative therapies in this patient population. IVS has been considered as a model for further understanding the molecular and cellular processes of spermatogenesis and as a potential regenerative therapeutic approach. While 2D cell cultures using human testicular cells have been attempted in previous research, lack of proper spatial arrangement limits germ cell differentiation and maturation, posing challenges for clinical application. Recent research suggests that 3D technology may have advantages for IVS due to mimicry of the native cytoarchitecture of human testicular tissue along with cell-cell communication directly or indirectly. 3D organotypic cultures, scaffolds, organoids, microfluidics, testis-on-a-chip, and bioprinting techniques have all shown potential to contribute to the technology of regenerative treatment strategies, including in vitro fertilization (IVF). Although promising, further work is needed to develop technology for successful, replicable, and safe IVS for humans. The intersection between tissue engineering, molecular biology, and reproductive medicine in IVS development allows for multidisciplinary involvement, where challenges can be overcome to realize regenerative therapies as a viable option.Copyright © 2024. Published by Elsevier Ltd.