Characterization of Nestin-positive stem Leydig cells as a potential source for the treatment of testicular Leydig cell dysfunction.
Characterization of Nestin-positive stem Leydig cells as a potential source for the treatment of testicular Leydig cell dysfunction.
复制标题
巢蛋白阳性干间质细胞作为治疗睾丸间质细胞功能障碍的潜在来源的表征。
作者：
从成人组织中识别和分离谱系特异性干细胞的能力可以促进细胞替代疗法。间质细胞（Leydig cell，LC）是哺乳动物睾丸中雄激素的主要来源，对间质干细胞（Stem Leydig cell，SLCs）的研究为睾酮缺乏症的治疗提供了新的可能。在此，在巢蛋白（内斯）启动子驱动的表达GFP的转基因小鼠模型中，我们观察到Nes-GFP+细胞位于SLC通常驻留的睾丸间质区室中。我们发现，这些Nes-GFP+细胞表达LIFR和PDGFR-α，但不表达LC谱系标志物。我们进一步观察到，这些细胞能够在体外进行克隆性自我更新和广泛增殖，并且可以分化为神经或间充质细胞谱系以及LC，在规定的条件下具有产生睾酮的能力。此外，当移植到LC破坏或衰老模型的睾丸中时，Nes-GFP+细胞定殖于睾丸并部分增加睾酮的产生，然后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，CD 51可能是一个假定的细胞表面标记的SLC，类似于巢蛋白。总之，这些结果表明，Nes-GFP+细胞从睾丸具有SLC的特性，我们的研究将开发干细胞替代疗法睾酮缺乏症的新的光。
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.
登录
查看更多内容
影响因子：
7.5
作者：
Gharaibeh B;Lavasani M;Cummins JH;Huard J
通讯作者：
Huard J
DOI：
10.1083/jcb.200409107
发表时间：
2004-12-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Davidoff MS;Middendorff R;Enikolopov G;Riethmacher D;Holstein AF;Müller D
通讯作者：
Müller D
影响因子：
4.8
作者：
Kaltschmidt, Barbara;Kaltschmidt, Christian;Widera, Darius
通讯作者：
Widera, Darius
影响因子：
7.3
作者：
Li, Q;Yu, Y;Olsen, BR
通讯作者：
Olsen, BR
影响因子：
2.5
作者：
Davidoff, MS;Middendorff, R;Holstein, AF
通讯作者：
Holstein, AF