ADSCs移植改善衰老睾丸间质细胞功能的作用及相关ERK/Wnt/TGFβ1机制的研究

With aging and the development of chemical industry, secretion of androgens (testosterone) deficiency disease incidence increased with years. The application of Leydig cells (LCs) transplantation is limited. To investigate a kind of cells, which is safe and feasible to self-renewal and differentiate to mature LCs, will be able to a new treatment options. In recent years, Adipose-derived stem cells (ADSCs) have been found the stronger ability to differentiate to steroid secreting cells. This indicated that ADSCs could treat senile disease and male hormone deficiency. Our previous studies have found that transplanted ADSCs could reverse age-related testosterone levels decreased, stimulate gonad reproductive function, improve the testicular function of aging rat. ADSCs transplantation may play a very important role in ameliorating age testicular dysfunction. However, at present cell factors and mechanism of the corresponding signal in regulating testicular function is not clear. Therefore this study investigate the role of ADSCs transplantation in development and function of aging leydig cells, secretion of testosterone and its signal mechanism by using D- galactose induced aging model and leydig cells、ADSCs in vitro culture techniques. And to further explore that the ERK signaling, Wnt/beta- catenin signaling and TGF- beta 1 / Smads signaling whether were involved in this process. This result will provide the research base for the problem of secretion of testosterone deficiency and aging testicular dysfunction, and provide experimental basis for stem cell aging theory and its application prospects.

随着老龄化及化工业的发展，雄激素(睾酮)分泌不足症发病率逐年增高。睾丸间质细胞（LCs）移植治疗能力有限，寻求一种安全可行的能自我更新同时可分化成熟的LCs，将能提供一种新的治疗方案。近年发现脂肪源干细胞（ADSCs）分化为类固醇分泌细胞的能力显著，提示应用ADSCs可治疗老年性、疾病性雄性激素不足。本课题组前期发现ADSCs移植可逆转增龄性大鼠睾丸激素水平下降，刺激性腺的生殖功能，提示其在治疗睾丸功能障碍的过程中可能扮演很重要的作用。而关于其调节睾丸功能的细胞因子和相应的信号机制尚不清楚。本项目利用D-半乳糖衰老模型及LCs、ADSCs培养技术，探讨ADSCs移植在LCs发育和睾酮分泌过程中的具体作用及其信号机制，并探讨ERK、Wnt/β-catenin、TGF-β1/Smads是否参与此过程，从而为解决睾酮分泌不足、睾丸功能障碍提供思路及研究基础，为干细胞抗衰老提供实验基础及应用前景。

随着老龄化及化工业的发展，雄激素(睾酮)分泌不足症发病率逐年增高。睾丸间质细胞（LCs）移植治疗能力有限，寻求一种安全可行的能自我更新同时可分化成熟的LCs，将能提供一种新的治疗方案。近年发现脂肪源干细胞（ADSCs）分化为类固醇分泌细胞的能力显著，提示应用ADSCs可治疗老年性、疾病性雄性激素不足。本课题组利用D-半乳糖衰老模型及LCs、ADSCs培养技术，探讨ADSCs移植在LCs发育和睾酮分泌过程中的具体作用及其信号机制。结果发现ADSCs移植可逆转增龄性大鼠睾丸激素水平下降，刺激性腺的生殖功能，提示其在治疗睾丸功能障碍的过程中可能扮演很重要的作用; 应用脂肪干细胞可以治疗老年性及疾病性雄性激素不足。研究进一步证实ADSCs移植在睾丸间质细胞发生发育和睾酮分泌过程中的具有保护衰老睾丸间质细胞的抗凋亡、促睾酮分泌的作用，这一过程可能与下调ERK等通路的调节相关，从而为解决睾酮分泌不足及衰老性睾丸功能障碍提供思路及研究基础，为干细胞抗衰老理论提供实验基础及应用前景。