利用诱导多能干细胞进行体外配子发生建模:综述
Modelling in vitro gametogenesis using induced pluripotent stem cells: a review.
作者信息
Romualdez-Tan Maria Victoria
机构信息
Present Address: Repro Optima Center for Reproductive Health, Inc., Ground Floor JRDC Bldg. Osmena Blvd. Capitol Site, Cebu City, 6000, Philippines.
Cebu Doctors University Hospital, Cebu City, Philippines.
出版信息
Cell Regen. 2023 Oct 16;12(1):33. doi: 10.1186/s13619-023-00176-5.
In vitro gametogenesis (IVG) has been a topic of great interest in recent years not only because it allows for further exploration of mechanisms of germ cell development, but also because of its prospect for innovative medical applications especially for the treatment of infertility. Elucidation of the mechanisms underlying gamete development in vivo has inspired scientists to attempt to recapitulate the entire process of gametogenesis in vitro. While earlier studies have established IVG methods largely using pluripotent stem cells of embryonic origin, the scarcity of sources for these cells and the ethical issues involved in their use are serious limitations to the progress of IVG research especially in humans. However, with the emergence of induced pluripotent stem cells (iPSCs) due to the revolutionary discovery of dedifferentiation and reprogramming factors, IVG research has progressed remarkably in the last decade. This paper extensively reviews developments in IVG using iPSCs. First, the paper presents key concepts from groundwork studies on IVG including earlier researches demonstrating that IVG methods using embryonic stem cells (ESCs) also apply when using iPSCs. Techniques for the derivation of iPSCs are briefly discussed, highlighting the importance of generating transgene-free iPSCs with a high capacity for germline transmission to improve efficacy when used for IVG. The main part of the paper discusses recent advances in IVG research using iPSCs in various stages of gametogenesis. In addition, current clinical applications of IVG are presented, and potential future applications are discussed. Although IVG is still faced with many challenges in terms of technical issues, as well as efficacy and safety, novel IVG methodologies are emerging, and IVG using iPSCs may usher in the next era of reproductive medicine sooner than expected. This raises both ethical and social concerns and calls for the scientific community to cautiously develop IVG technology to ensure it is not only efficacious but also safe and adheres to social and ethical norms.
体外配子发生(IVG)近年来一直是备受关注的话题,这不仅是因为它有助于进一步探索生殖细胞发育机制,还因其在创新医学应用方面的前景,尤其是在不孕症治疗领域。对体内配子发育潜在机制的阐明激发了科学家尝试在体外重现配子发生的全过程。早期研究主要利用胚胎来源的多能干细胞建立了IVG方法,但这些细胞来源稀缺以及使用过程中涉及的伦理问题严重限制了IVG研究的进展,尤其是在人类研究方面。然而,由于去分化和重编程因子的革命性发现,诱导多能干细胞(iPSC)应运而生,在过去十年中,IVG研究取得了显著进展。本文广泛回顾了利用iPSC进行IVG的进展。首先,本文介绍了IVG基础研究的关键概念,包括早期研究表明使用胚胎干细胞(ESC)的IVG方法在使用iPSC时同样适用。简要讨论了iPSC的诱导技术,强调了生成无转基因且具有高生殖系传递能力的iPSC对于提高IVG应用效果的重要性。本文的主要部分讨论了利用iPSC在配子发生各个阶段进行IVG研究的最新进展。此外,还介绍了IVG目前的临床应用,并探讨了其未来潜在应用。尽管IVG在技术问题、有效性和安全性方面仍面临诸多挑战,但新的IVG方法不断涌现,利用iPSC的IVG可能比预期更早地引领生殖医学进入下一个时代。这引发了伦理和社会关注,呼吁科学界谨慎开发IVG技术,以确保其不仅有效,而且安全,并符合社会和伦理规范。
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