title: Characterization of Nestin-positive stem Leydig cells as a potential source for the treatment of testicular Leydig cell dysfunction.
abstract: 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 identification 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-α, 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.
authors.affiliation: 1] Cell-gene Therapy Translational Medicine Research Center, The Third Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510630, China [2] Key Laboratory for Stem Cells and Tissue Engineering, Center for Stem Cell Biology and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong 510080, China [3] Department of Anatomy, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
authors.forename: Mei Hua
authors.initials: MH
authors.lastname: Jiang
authors.affiliation: 1] Key Laboratory for Stem Cells and Tissue Engineering, Center for Stem Cell Biology and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong 510080, China [2] Reproductive Medicine Center and Guangdong provincial Key Laborartory of Reproductive Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Cai
authors.affiliation: 1] Key Laboratory for Stem Cells and Tissue Engineering, Center for Stem Cell Biology and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong 510080, China [2] Department of Histopathology,The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Tuo
authors.affiliation: Key Laboratory for Stem Cells and Tissue Engineering, Center for Stem Cell Biology and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
authors.forename: Jiancheng
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Infertility and Sexual Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510630, China.
authors.forename: Zhi Jun
authors.initials: ZJ
authors.lastname: Zang
authors.affiliation: Department of Urology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China.
authors.forename: Xiang'an
authors.initials: X
authors.lastname: Tu
authors.affiliation: Reproductive Medicine Center and Guangdong provincial Key Laborartory of Reproductive Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Key Laboratory of Bioengineering Medicine of Guangdong Province, Institute of Biomedicine, Jinan University, Guangzhou, Guangdong 510632, China.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Su
authors.affiliation: 1] Key Laboratory for Stem Cells and Tissue Engineering, Center for Stem Cell Biology and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong 510080, China [2] Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
authors.forename: Weiqiang
authors.initials: W
authors.lastname: Li
authors.affiliation: Key Laboratory for Stem Cells and Tissue Engineering, Center for Stem Cell Biology and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
authors.forename: Guilan
authors.initials: G
authors.lastname: Li
authors.affiliation: Key Laboratory for Stem Cells and Tissue Engineering, Center for Stem Cell Biology and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: State key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Jiao
authors.affiliation: Department of Urology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China.
authors.forename: Zi
authors.initials: Z
authors.lastname: Wan
authors.affiliation: Department of Urology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Deng
authors.affiliation: Key Laboratory for Stem Cells and Tissue Engineering, Center for Stem Cell Biology and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
authors.forename: Bruce T
authors.initials: BT
authors.lastname: Lahn
authors.affiliation: 1] Cell-gene Therapy Translational Medicine Research Center, The Third Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510630, China [2] Key Laboratory for Stem Cells and Tissue Engineering, Center for Stem Cell Biology and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong 510080, China [3] Department of Anatomy, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, China [4] Reproductive Medicine Center and Guangdong provincial Key Laborartory of Reproductive Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, China [5] Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
authors.forename: Andy Peng
authors.initials: AP
authors.lastname: Xiang
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D000375:Aging; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D015870:Gene Expression; D039564:Integrin alphaV / Q000032:analysis; D007985:Leydig Cells / Q000166:cytology / Q000378:metabolism / Q000473:pathology* / Q000637:transplantation*; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D064231:Nestin / Q000032:analysis* / Q000235:genetics; D011446:Prospective Studies; D013091:Spermatogenesis; D013737:Testis / Q000166:cytology* / Q000473:pathology* / Q000502:physiology; D013739:Testosterone / Q000378:metabolism
chemical_list: D039564:Integrin alphaV; D064231:Nestin; D013739:Testosterone