de Bruin Ilse J, Spaander Merel M, Harmsen Simone, Edelenbosch Rosanne, Ploem M Corrette, Dartée Nina, Cardoso Vaz Santos Madalena, Lakshmipathi Mathangi, Mulder Callista L, van Pelt Ans M M, Baarends Willy M, Chuva de Sousa Lopes Susana M, de Wert Guido M W R, Segers Seppe, Hamer Geert, Pereira Daoud Ana M
Department of Developmental Biology, Erasmus MC, Rotterdam, The Netherlands.
Department of Health Law, University of Amsterdam, Amsterdam, The Netherlands.
Hum Reprod. 2025 Sep 1;40(9):1605-1615. doi: 10.1093/humrep/deaf123.
Stem cell-derived (SCD)-gametes derived from induced or autologous (i.e. patient-specific) cells may help mitigate human fertility problems caused by physiological or social factors in the (near) future. While this technology is still in its infancy, recent advancements with SCD-gametes generated from mouse pluripotent stem cells have led some researchers to expect-and investors to anticipate-the clinical introduction of human gametes derived from induced pluripotent stem cells (iPSCD-gametes) within two decades. However, it remains to be investigated how realistic these expectations are, and how they would balance against careful consideration of technical, ethical, legal, and societal aspects, including-but not limited to-safety and effectiveness. This mini-review aims to encourage that investigation by providing a brief overview of the state-of-the-art and highlighting the breadth of issues involved in the potential clinical introduction of human iPSCD-gametes. These issues emerge before (Stage 1), during (Stage 2), and after (Stage 3) clinical trials, and are discussed in that order. Issues discussed in the context of Stage 1 suggest that gathering the evidence required to preclinically assess the safety of human iPSCD-gametes will be time-consuming and require parallel experiments with sensitive research materials. Issues discussed in the context of Stage 2 suggest that it might take several years for human iPSCD-gametes to transition through distinct clinical trial phases, and that inevitable (and unforeseeable) variations in the quality of human iPSCD-gametes are likely to further slow this down. Finally, issues discussed in the context of Stage 3 suggest that offering human iPSCD-gametes clinically will require addressing questions of accountability and monitoring, some of which might be difficult to formalize by law. Combined, these findings suggest that a responsible clinical introduction of human iPSCD-gametes may take considerably longer than expected, underscoring the importance of transdisciplinary collaborations with a broad range of stakeholders to make well-informed and well-considered choices about their development and application.
源自诱导或自体（即患者特异性）细胞的干细胞衍生（SCD）配子可能在（不久的）将来有助于缓解由生理或社会因素引起的人类生育问题。虽然这项技术仍处于起步阶段，但最近从小鼠多能干细胞生成SCD配子方面取得的进展已使一些研究人员有所期待，也让投资者预期在二十年内将源自诱导多能干细胞的人类配子（iPSCD配子）引入临床。然而，这些期望有多现实，以及它们如何与对技术、伦理、法律和社会方面（包括但不限于安全性和有效性）的审慎考虑相平衡，仍有待研究。本综述旨在通过简要概述当前技术水平并强调人类iPSCD配子潜在临床应用中涉及的广泛问题来推动这项研究。这些问题出现在临床试验之前（第1阶段）、期间（第2阶段）和之后（第3阶段），并按此顺序进行讨论。在第1阶段背景下讨论的问题表明，收集临床前评估人类iPSCD配子安全性所需的证据将耗时长久，并且需要使用敏感研究材料进行平行实验。在第2阶段背景下讨论的问题表明，人类iPSCD配子可能需要数年时间才能完成不同的临床试验阶段，而且人类iPSCD配子质量不可避免（且不可预见）的差异可能会进一步减缓这一进程。最后，在第3阶段背景下讨论的问题表明，在临床中提供人类iPSCD配子将需要解决问责和监测问题，其中一些问题可能难以通过法律形式化。综合来看，这些发现表明，人类iPSCD配子的负责任临床应用可能比预期耗时长得多，这凸显了与广泛利益相关者开展跨学科合作对于就其开发和应用做出明智且周全选择的重要性。
