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Advances in stem cell research for the treatment of primary hypogonadism
Nature Reviews Urology ( IF 15.3 ) Pub Date : 2021-06-29 , DOI: 10.1038/s41585-021-00480-2
Lu Li 1 , Vassilios Papadopoulos 1
Affiliation  

In Leydig cell dysfunction, cells respond weakly to stimulation by pituitary luteinizing hormone, and, therefore, produce less testosterone, leading to primary hypogonadism. The most widely used treatment for primary hypogonadism is testosterone replacement therapy (TRT). However, TRT causes infertility and has been associated with other adverse effects, such as causing erythrocytosis and gynaecomastia, worsening obstructive sleep apnoea and increasing cardiovascular morbidity and mortality risks. Stem-cell-based therapy that re-establishes testosterone-producing cell lineages in the body has, therefore, become a promising prospect for treating primary hypogonadism. Over the past two decades, substantial advances have been made in the identification of Leydig cell sources for use in transplantation surgery, including the artificial induction of Leydig-like cells from different types of stem cells, for example, stem Leydig cells, mesenchymal stem cells, and pluripotent stem cells (PSCs). PSC-derived Leydig-like cells have already provided a powerful in vitro model to study the molecular mechanisms underlying Leydig cell differentiation and could be used to treat men with primary hypogonadism in a more specific and personalized approach.



中文翻译:

干细胞治疗原发性性腺功能减退症的研究进展

在 Leydig 细胞功能障碍中,细胞对垂体黄体生成素的刺激反应较弱,因此产生较少的睾酮,导致原发性性腺功能减退症。原发性性腺功能减退症最广泛使用的治疗方法是睾酮替代疗法 (TRT)。然而,TRT 会导致不孕,并与其他不良反应相关,例如引起红细胞增多症和男子女性型乳房发育、阻塞性睡眠呼吸暂停恶化以及心血管疾病发病率和死亡率风险增加。因此,基于干细胞的疗法可在体内重建产生睾酮的细胞谱系,因此成为治疗原发性性腺功能减退症的一个有希望的前景。在过去的二十年里,在移植手术中使用的 Leydig 细胞来源的鉴定方面取得了实质性进展,包括从不同类型的干细胞中人工诱导 Leydig 样细胞,例如干 Leydig 细胞、间充质干细胞和多能干细胞 (PSC)。PSC 衍生的 Leydig 样细胞已经提供了一个强大的体外模型来研究 Leydig 细胞分化的分子机制,并可用于以更具体和个性化的方法治疗患有原发性性腺功能减退症的男性。

更新日期:2021-06-29
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