应用脂肪间充质干细胞分化的睾丸间质细胞和生物材料支架构建雄激素分泌组织

项目名称： 应用脂肪间充质干细胞分化的睾丸间质细胞和生物材料支架构建雄激素分泌组织

项目编号： No.30870650

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 生物科学

项目作者： 魏星

作者单位： 暨南大学

项目金额： 29万元

中文摘要： 雄激素缺乏症严重地影响了中老年男性的健康，目前尚无理想的疗法，细胞治疗代表未来的发展趋势。本项目比较了不同的方法（包括共培养，采用诱导剂和采用SF-1基因等），将间充质干细胞（MSCs）诱导分化为睾丸间质细胞。与其他方法相比，SF-1基因能够更有效地将MSCs诱导分化为睾丸间质细胞。采用含有SF-1基因的腺病毒感染人脐带间充质干细胞（UC-MSCs），在含有10%胎牛血清和500μcAMP的培养液内培养7天，本项目首次成功地将UC-MSCs诱导分化为睾丸间质细胞，分化的细胞能够高水平地表达类固醇合成相关基因，包括P450scc，3βSD，17βSD，LH-R，ACTH-R和P450c21，能够分泌高水平的睾酮。 本项目还首次表明，与人骨髓间充质干细胞（BM-MSCs）相比，UC-MSCs具有显著更强地向睾丸间质细胞分化的能力。UC-MSCs还具有增值能力强，易获得和免疫原性低，移植后不易被排斥等优点。此项目具有重要的理论和应用价值，UC-MSCs可为治疗多种人雄激素缺乏症提供理想的种子细胞来源。已在国际高水平期刊发表SCI论文3篇，被接受SCI论文1篇，已申报发明专利1项。

中文关键词： 组织工程；间充质干细胞；多能性；基因表达

英文摘要： Androgen deficiency seriously affects the life quality of the aging male, no effective treatment currently is available for this disease, and cell transplantation can be future direction for the treatment of this disease. This study compared different methods (including co-culture, the use of inducer and the use of SF-1 gene) and induced mesenchymal stem cells (MSCs) to differentiate into Leydig cells. Compared with the other methods, SF-1 gene could more effectively induce MSCs to differentiate into Leydig cells. By using adenovirus containing SF-1 gene to infect MSCs derived from umbilical cord (UC-MSCs) and culturing UC-MSCs for 7 days in the presence of 10% FBS and 500μcAMP, UC-MSCs were successfully induced to differentiate into Leydig cells for the first time. The differentiated cells showed high expression of the steroidogenic mRNAs, including P450scc，3βSD，17βSD，LH-R，ACTH-R and P450c21 and secreted high level of testosterone. For the first time, this study also demonstrated that UC-MSCs had significantly higher potential of Leydig cell differentiation than BM-MSCs. UC-MSCs can rapidly proliferate and can be easily isolated and have low immunogenicity so that they are less likely rejected after their transplantation. This study has important theoretical and applied values and UC-MSCs can be ideal cell choice for cell-based therapy for androgen deficiency. In this study, 3 SCI papers were published in the prestigious journals, 1 SCI paper was accepted, and 1 patent was applied.

英文关键词： tissue engineering; mesenchymal stem cells; multipotency; gene expression