Directed mouse embryonic stem cells into leydig-like cells rescue testosterone-deficient male rats in vivo.
Directed mouse embryonic stem cells into leydig-like cells rescue testosterone-deficient male rats in vivo.
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DOI：
10.1089/scd.2014.0370
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发表时间：
2015-02
影响因子：
4
通讯作者：
Yan Yang;Zhijian Su;Wenting Xu;Jiao Luo;Rui Liang;Q. Xiang;Qi‐hao Zhang;R. Ge;Yadong Huang-Yadong-Huan
中科院分区：
文献类型：
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作者：
Yan Yang;Zhijian Su;Wenting Xu;Jiao Luo;Rui Liang;Q. Xiang;Qi‐hao Zhang;R. Ge;Yadong Huang-Yadong-Huan
Leydig细胞的主要功能是分泌睾酮，这在男性生殖和发育的调节中至关重要。睾丸激素水平低会导致男性性腺功能减退。干细胞来源的间质细胞移植可能是治疗男性性腺功能减退症的一种有前途的替代疗法。到目前为止，其他人已经报道Leydig样细胞可以来源于间充质干细胞、胚胎干细胞（ESC）和诱导多能干细胞。然而，分化的Leydig细胞的效率仍然很低，并且产生功能性成体Leydig细胞（ALCs）的进展有限。在此，我们描述了一种通过转录因子类固醇生成因子-1（SF-1）的过表达和用8-溴腺苷-3 '，5'-环一磷酸和毛喉素的组合处理来指导小鼠胚胎干细胞（mESC）体外分化为Leydig样细胞的稳健方法。这些分化的细胞表达编码类固醇生成酶的mRNA并产生孕酮和睾酮。重要的是，当移植到雄性大鼠中时，它们的原始Leydig细胞被乙烯二甲磺酸盐选择性地消除，这些体外衍生的Leydig样细胞进一步发育成功能性ALC，拯救血清睾酮水平。这些数据提供了mESC可以在体外诱导分化为Leydig样细胞的证据，其可以在体内微环境中发育。
The primary function of Leydig cells is to secrete testosterone, which is critical in the regulation of male reproduction and development. Low levels of testosterone will lead to male hypogonadism. Stem cell-derived Leydig cell transplantation may be a promising alternative therapy for male hypogonadism. Thus far, others have reported that Leydig-like cells can be derived from mesenchymal stem cells, embryonic stem cells (ESCs), and induced pluripotent stem cells. However, the efficiency of the differentiating Leydig cells remains low, and progress toward generating functional adult Leydig cells (ALCs) is limited. Herein, we describe a robust method of directing differentiation of mouse embryonic stem cells (mESCs) into Leydig-like cells in vitro by overexpression of the transcription factor steroidogenic factor-1 (SF-1) and treatment with a combination of 8-Bromoadenosine-3',5'-cyclic monophosphate and forskolin. These differentiated cells express mRNA encoding the steroidogenic enzymes and produce progesterone and testosterone. Importantly, when transplanted into male rats that had their original Leydig cells selectively eliminated by ethylene dimethanesulfonate, these in vitro-derived Leydig-like cells further developed into functional ALCs that rescued serum testosterone levels. These data provide evidence that mESCs can be induced to differentiate into Leydig-like cells in vitro, which can develop in the in vivo microenvironment.