Androgen deficiency (hypogonadism) affects males of all ages. Testosterone replacement therapy (TRT) is effective in restoring serum testosterone and relieving symptoms. TRT, however, is reported to have possible adverse effects in part because administered testosterone is not produced in response to the hypothalamic-pituitary-gonadal (HPG) axis. Progress in stem cell biology offers potential alternatives for treating hypogonadism. Adult Leydig cells (ALCs) are generated by stem Leydig cells (SLCs) during puberty. SLCs persist in the adult testis. Considerable progress has been made in the identification, isolation, expansion and differentiation of SLCs in vitro. In addition to forming ALCs, SLCs are multipotent, with the ability to give rise to all 3 major cell lineages of typical mesenchymal stem cells, including osteoblasts, adipocytes, and chondrocytes. Several regulatory factors, including Desert hedgehog and platelet-derived growth factor, have been reported to play key roles in the proliferation and differentiation of SLCs into the Leydig lineage. In addition, stem cells from several nonsteroidogenic sources, including embryonic stem cells, induced pluripotent stem cells, mature fibroblasts, and mesenchymal stem cells from bone marrow, adipose tissue, and umbilical cord have been transdifferentiated into Leydig-like cells under a variety of induction protocols. ALCs generated from SLCs in vitro, as well as Leydig-like cells, have been successfully transplanted into ALC-depleted animals, restoring serum testosterone levels under HPG control. However, important questions remain, including: How long will the transplanted cells continue to function? Which induction protocol is safest and most effective? For translational purposes, more work is needed with primate cells, especially human.

中文翻译：

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成人睾丸中的干 Leydig 细胞：表征、调节和潜在应用。

雄激素缺乏症（性腺机能减退）影响所有年龄段的男性。睾酮替代疗法 (TRT) 可有效恢复血清睾酮和缓解症状。然而，据报道 TRT 可能有副作用，部分原因是给药的睾酮不是对下丘脑 - 垂体 - 性腺 (HPG) 轴产生反应。干细胞生物学的进展为治疗性腺功能减退症提供了潜在的替代方案。成年 Leydig 细胞 (ALC) 是在青春期由干 Leydig 细胞 (SLC) 产生的。SLC 持续存在于成人睾丸中。在体外 SLC 的鉴定、分离、扩增和分化方面取得了相当大的进展。除了形成 ALC 外，SLC 还具有多能性，能够产生典型间充质干细胞的所有 3 种主要细胞谱系，包括成骨细胞、脂肪细胞、和软骨细胞。据报道，包括沙漠刺猬和血小板衍生生长因子在内的几种调节因子在 SLC 向 Leydig 谱系的增殖和分化中起关键作用。此外，来自多种非类固醇来源的干细胞，包括胚胎干细胞、诱导多能干细胞、成熟成纤维细胞和骨髓、脂肪组织和脐带的间充质干细胞，已在多种诱导下转分化为 Leydig 样细胞。协议。从体外 SLC 产生的 ALC 以及 Leydig 样细胞已成功移植到 ALC 耗尽的动物中，在 HPG 控制下恢复血清睾酮水平。然而，重要的问题仍然存在，包括：移植的细胞还能继续发挥作用多久？哪种诱导方案最安全、最有效？出于翻译目的，灵长类动物细胞，尤其是人类细胞需要做更多的工作。