Characterization of Nestin-positive stem Leydig cells as a potential source for the treatment of testicular Leydig cell dysfunction

• Published in: Cell research Vol. 24; no. 12; pp. 1466 - 1485
• Main Authors: Jiang, Mei Hua, Cai, Bing, Tuo, Ying, Wang, Jiancheng, Zang, Zhi Jun, Tu, Xiang'an, Gao, Yong, Su, Zhijian, Li, Weiqiang, Li, Guilan, Zhang, Min, Jiao, Jianwei, Wan, Zi, Deng, Chunhua, Lahn, Bruce T, Xiang, Andy Peng
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.12.2014; Nature Publishing Group
• Subjects: 631/337; 692/699/2743/2730; 692/700/565; Adult Stem Cells - cytology; Adult Stem Cells - metabolism; Adult Stem Cells - transplantation; Aging; Animals; Biomedical and Life Sciences; Cell Biology; Cell Differentiation; Cell Proliferation; Cells, Cultured; Gene Expression; Integrin alphaV - analysis; Leydig Cells - cytology; Leydig Cells - metabolism; Leydig Cells - pathology; Leydig Cells - transplantation; Leydig细胞; Life Sciences; Male; Mammals; Mice, Inbred C57BL; Mice, Transgenic; Nestin - analysis; Nestin - genetics; Original; original-article; Prospective Studies; Spermatogenesis; Stem cells; Testis - cytology; Testis - pathology; Testis - physiology; Testosterone - metabolism; 功能障碍; 巢蛋白; 治疗; 睾丸间质细胞; 表征; 转基因小鼠模型; 阳性; stem Leydig cell; Leydig cell dysfunction; Nestin; multipotency; self-renewal
• ISSN: 1001-0602; 1748-7838
• DOI: 10.1038/cr.2014.149

The ability to identify and isolate lineage-specific stem cells from adult tissues could facilitate cell replacement therapy. Leydig cells （LCs） are the primary source of androgen in the mammalian testis, and the prospective iden- tification of stem Leydig cells （SLCs） may offer new opportunities for treating testosterone deficiency. Here, in a transgenic mouse model expressing GFP driven by the Nestin （Nes） promoter, we observed Nes-GFP~ cells located in the testicular interstitial compartment where SLCs normally reside. We showed that these Nes-GFP~ cells expressed LIFR and PDGFR-e, but not LC lineage markers. We further observed that these cells were capable of clonogenic self-renewal and extensive proliferation in vitro and could differentiate into neural or mesenchymal cell lineages, as well as LCs, with the ability to produce testosterone, under defined conditions. Moreover, when transplanted into the testes of LC-disrupted or aging models, the Nes-GFP＋ cells colonized the interstitium and partially increased testosterone production, and then accelerated meiotic and post-meiotic germ cell recovery. In addition, we further demonstrated that CD51 might be a putative cell surface marker for SLCs, similar with Nestin. Taken together, these results suggest that Nes-GFP~ cells from the testis have the characteristics of SLCs, and our study would shed new light on developing stem cell replacement therapy for testosterone deficiency.