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首页> 美国卫生研究院文献>Cell Research >Characterization of Nestin-positive stem Leydig cells as a potential source for the treatment of testicular Leydig cell dysfunction
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Characterization of Nestin-positive stem Leydig cells as a potential source for the treatment of testicular Leydig cell dysfunction

机译：Nestin阳性干Leydig细胞的表征可作为治疗睾丸Leydig细胞功能障碍的潜在来源

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The ability to identify and isolate lineage-specific stem cells from adult tissues could facilitate cell replacement therapy. Leydig cells (LCs) are the primary source of androgen in the mammalian testis, and the prospective identification of stem Leydig cells (SLCs) may offer new opportunities for treating testosterone deficiency. Here, in a transgenic mouse model expressing GFP driven by the Nestin (Nes) promoter, we observed Nes-GFP+ cells located in the testicular interstitial compartment where SLCs normally reside. We showed that these Nes-GFP+ cells expressed LIFR and PDGFR-α, but not LC lineage markers. We further observed that these cells were capable of clonogenic self-renewal and extensive proliferation in vitro and could differentiate into neural or mesenchymal cell lineages, as well as LCs, with the ability to produce testosterone, under defined conditions. Moreover, when transplanted into the testes of LC-disrupted or aging models, the Nes-GFP+ cells colonized the interstitium and partially increased testosterone production, and then accelerated meiotic and post-meiotic germ cell recovery. In addition, we further demonstrated that CD51 might be a putative cell surface marker for SLCs, similar with Nestin. Taken together, these results suggest that Nes-GFP+ cells from the testis have the characteristics of SLCs, and our study would shed new light on developing stem cell replacement therapy for testosterone deficiency.
机译：从成年组织中鉴定和分离谱系特异性干细胞的能力可以促进细胞替代治疗。 Leydig细胞（LCs）是哺乳动物睾丸中雄激素的主要来源，干Leydig干细胞（SLCs）的前瞻性鉴定可能为治疗睾丸激素缺乏症提供新的机会。在此，在表达由Nestin（Nes）启动子驱动的GFP的转基因小鼠模型中，我们观察到位于SLC正常存在的睾丸间质区的Nes-GFP + 细胞。我们发现这些Nes-GFP + 细胞表达LIFR和PDGFR-α，但不表达LC谱系标记。我们进一步观察到，这些细胞在体外能够克隆形成自我更新和广泛增殖，并且可以在限定条件下分化为神经或间充质细胞谱系以及LC，并具有产生睾丸激素的能力。而且，当Nes-GFP + 细胞移植到LC破坏或衰老模型的睾丸中时，它会在间质中定殖并部分增加睾丸激素的产生，从而加速减数分裂和减数分裂后生殖细胞的恢复。此外，我们进一步证明CD51可能是SLC的推定细胞表面标记，与Nestin相似。综上所述，这些结果表明来自睾丸的Nes-GFP + 细胞具有SLCs的特征，我们的研究将为开发用于睾丸激素缺乏症的干细胞替代疗法提供新的思路。

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