Transplantation of CD51+ Stem Leydig Cells: A New Strategy for the Treatment of Testosterone Deficiency

睾酮(贴片) 移植 干细胞 生物 间质细胞 促黄体激素 间充质干细胞 雄激素 精子发生 内分泌学 内科学 激素 医学 细胞生物学
作者
Zhi Jun Zang,Jiancheng Wang,Zhihong Chen,Yan Zhang,Yong Gao,Zhijian Su,Ying Tuo,Yan Liao,Min Zhang,Qunfang Yuan,Chunhua Deng,Meihua Jiang,Andy Peng Xiang
出处
期刊:Stem Cells [Wiley]
卷期号:35 (5): 1222-1232 被引量:56
标识
DOI:10.1002/stem.2569
摘要

Abstract Stem Leydig cell (SLC) transplantation could provide a new strategy for treating the testosterone deficiency. Our previous study demonstrated that CD51 (also called integrin αv) might be a putative cell surface marker for SLCs, but the physiological function and efficacy of CD51+ SLCs treatment remain unclear. Here, we explore the potential therapeutic benefits of CD51+ SLCs transplantation and whether these transplanted cells can be regulated by the hypothalamic-pituitary-gonadal (HPG) axis. CD51+ cells were isolated from the testes of 12-weeks-old C57BL/6 mice, and we showed that such cells expressed SLC markers and that they were capable of self-renewal, extensive proliferation, and differentiation into multiple mesenchymal cell lineages and LCs in vitro. As a specific cytotoxin that eliminates Leydig cells (LCs) in adult rats, ethane dimethanesulfonate (EDS) was used to ablate LCs before the SLC transplantation. After being transplanted into the testes of EDS-treated rats, the CD51+ cells differentiated into mature LCs, and the recipient rats showed a partial recovery of testosterone production and spermatogenesis. Notably, a testosterone analysis revealed a circadian rhythm of testosterone secretion in cell-transplanted rats, and these testosterone secretions could be suppressed by decapeptyl (a luteinizing hormone-releasing hormone agonist), suggesting that the transplanted cells might be regulated by the HPG axis. This study is the first to demonstrate that CD51+ SLCs can restore the neuroendocrine regulation of testicular function by physiologically recovering the expected episodic changes in diurnal testosterone serum levels and that SLC transplantation may provide a new tool for the studies of testosterone deficiency treatment.
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