Transplanted human p75-positive stem Leydig cells replace disrupted Leydig cells for testosterone production.
Transplanted human p75-positive stem Leydig cells replace disrupted Leydig cells for testosterone production.
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DOI：
10.1038/cddis.2017.531
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发表时间：
2017-10-12
影响因子：
9
通讯作者：
Xiang AP
中科院分区：
文献类型：
--
作者：
Zhang M;Wang J;Deng C;Jiang MH;Feng X;Xia K;Li W;Lai X;Xiao H;Ge RS;Gao Y;Xiang AP
已有研究表明，啮齿类动物间质干细胞（SLC）移植可部分恢复睾丸间质细胞（LC）破坏或衰老动物模型的睾酮分泌，为性腺功能减退症的治疗提供了一种有前景的方法。在这里，我们前瞻性地分离人SLC，并探索人SLC移植治疗性腺功能减退症的潜在治疗益处。在成人睾丸中，p75神经营养因子受体阳性（p75+）细胞表达已知的SLC标记物巢蛋白，但不表达LC谱系标记物羟基类固醇脱氢酶-3 β（HSD 3 β）。流式细胞仪分选出的p75+细胞在体外能扩增并具有克隆性自我更新能力。p75+细胞在体外具有向多个中胚层细胞谱系和产生睾酮的LC的多谱系分化潜能。将p75+细胞移植到乙烷二甲烷磺酸盐（EDS）处理的LC破坏大鼠模型的睾丸中后，p75+细胞在体内分化为LC，并以生理模式分泌睾酮。此外，p75+细胞移植促进血清睾酮水平、精子发生和生殖器官重量的恢复。综上所述，我们报道了一种基于p75表达鉴定和分离人SLC的方法，并证明了移植的人p75+ SLC可以取代破坏的LC用于睾酮的产生。这些发现为进一步将人SLC用于性腺功能减退症的临床应用奠定了基础。
Previous studies have demonstrated that rodent stem Leydig cell (SLC) transplantation can partially restore testosterone production in Leydig cell (LC)-disrupted or senescent animal models, which provides a promising approach for the treatment of hypogonadism. Here, we isolated human SLCs prospectively and explored the potential therapeutic benefits of human SLC transplantation for hypogonadism treatment. In adult human testes, p75 neurotrophin receptor positive (p75+) cells expressed the known SLC marker nestin, but not the LC lineage marker hydroxysteroid dehydrogenase-3β (HSD3β). The p75+ cells which were sorted by flow cytometry from human adult testes could expand in vitro and exhibited clonogenic self-renewal capacity. The p75+ cells had multi-lineage differentiation potential into multiple mesodermal cell lineages and testosterone-producing LCs in vitro. After transplantation into the testes of ethane dimethane sulfonate (EDS)-treated LC-disrupted rat models, the p75+ cells differentiated into LCs in vivo and secreted testosterone in a physiological pattern. Moreover, p75+ cell transplantation accelerated the recovery of serum testosterone levels, spermatogenesis and reproductive organ weights. Taken together, we reported a method for the identification and isolation of human SLCs on the basis of p75 expression, and demonstrated that transplanted human p75+ SLCs could replace disrupted LCs for testosterone production. These findings provide the groundwork for further clinical application of human SLCs for hypogonadism.
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影响因子：
4.1
作者：
Chen H;Ge RS;Zirkin BR
通讯作者：
Zirkin BR
血浆睾丸激素水平的个体变异来源。
DOI：
10.1098/rstb.2007.0001
发表时间：
2008-05-12
影响因子：
6.3
作者：
Kempenaers, Bart;Peters, Anne;Foerster, Katharina
通讯作者：
Foerster, Katharina
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：
5.8
作者：
Srinath, Reshmi;Golden, Sherita Hill;Dobs, Adrian
通讯作者：
Dobs, Adrian
DOI：
10.1084/jem.20122252
发表时间：
2013-07-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Pinho S;Lacombe J;Hanoun M;Mizoguchi T;Bruns I;Kunisaki Y;Frenette PS
通讯作者：
Frenette PS