Center of Scientific Research, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, PR China.
Department of Gastroenetrology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, PR China.
J Cell Mol Med. 2019 Sep;23(9):5956-5969. doi: 10.1111/jcmm.14427. Epub 2019 Jul 10.
Leydig cells (LCs) are the primary source of testosterone in the testis, and testosterone deficiency caused by LC functional degeneration can lead to male reproductive dysfunction. LC replacement transplantation is a very promising approach for this disease therapy. Here, we report that human adipose derived stem cells (ADSCs) can be differentiated into Leydig-like cells using a novel differentiation method based on molecular compounds. The isolated human ADSCs expressed positive CD29, CD44, CD59 and CD105, negative CD34, CD45 and HLA-DR using flow cytometry, and had the capacity of adipogenic and osteogenic differentiation. ADSCs derived Leydig-like cells (ADSC-LCs) acquired testosterone synthesis capabilities, and positively expressed LC lineage-specific markers LHCGR, STAR, SCARB1, SF-1, CYP11A1, CYP17A1, HSD3B1 and HSD17B3 as well as negatively expressed ADSC specific markers CD29, CD44, CD59 and CD105. When ADSC-LCs labelled with lipophilic red dye (PKH26) were injected into rat testes which were selectively eliminated endogenous LCs using ethylene dimethanesulfonate (EDS, 75 mg/kg), the transplanted ADSC-LCs could survive and function in the interstitium of testes, and accelerate the recovery of blood testosterone levels and testis weights. These results demonstrated that ADSCs could be differentiated into Leydig-like cells by few defined molecular compounds, which might lay the foundation for further clinical application of ADSC-LC transplantation therapy.
间质细胞（LCs）是睾丸中睾酮的主要来源，LC 功能退化引起的睾酮缺乏可导致男性生殖功能障碍。LC 替代移植是治疗这种疾病的一种很有前途的方法。在这里，我们报告说，人脂肪来源的干细胞（ADSCs）可以通过一种基于分子化合物的新型分化方法分化为类间质细胞。分离的人 ADSCs 通过流式细胞术表达阳性 CD29、CD44、CD59 和 CD105，阴性 CD34、CD45 和 HLA-DR，具有成脂和成骨分化的能力。ADSC 衍生的类间质细胞（ADSC-LCs）获得了睾酮合成能力，并阳性表达 LC 谱系特异性标记 LHCGR、STAR、SCARB1、SF-1、CYP11A1、CYP17A1、HSD3B1 和 HSD17B3，以及阴性表达 ADSC 特异性标记 CD29、CD44、CD59 和 CD105。当用亲脂性红色染料（PKH26）标记的 ADSC-LCs 被注射到大鼠睾丸中时，大鼠睾丸通过乙撑二甲基磺酸盐（EDS，75mg/kg）选择性消除内源性 LCs，移植的 ADSC-LCs 可以在睾丸间质中存活并发挥作用，并加速血液睾酮水平和睾丸重量的恢复。这些结果表明，ADSCs 可以通过几种定义明确的分子化合物分化为类间质细胞，这可能为进一步的 ADSC-LC 移植治疗的临床应用奠定基础。
