title: Transplantation of CD51+Stem Leydig Cells: A New Strategy for the Treatment of Testosterone Deficiency.
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. Stem Cells 2017;35:1222-1232.
authors.affiliation: The Biological Therapy Center, The Third Affiliated Hospital, Guangzhou, China.|Department of Infertility and Sexual Medicine, The Third Affiliated Hospital, Guangzhou, China.|Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Guangzhou, China.
authors.forename: Zhi Jun
authors.initials: ZJ
authors.lastname: Zang
authors.affiliation: The Biological Therapy Center, The Third Affiliated Hospital, Guangzhou, China.|Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Guangzhou, China.
authors.forename: Jiancheng
authors.initials: J
authors.lastname: Wang
authors.affiliation: Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Guangzhou, China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Infertility and Sexual Medicine, The Third Affiliated Hospital, Guangzhou, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Reproductive Medicine Center and Guangdong provincial Key Laboratory of Reproductive Medicine, The First Affiliated Hospital, Guangzhou, 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, China.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Su
authors.affiliation: Department of Histopathology, The First Affiliated Hospital, Guangzhou, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Tuo
authors.affiliation: Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Guangzhou, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Guangzhou, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Anatomy, Zhongshan School of Medicine, Guangzhou, China.
authors.forename: Qunfang
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: Department of Urology, The First Affiliated Hospital, Guangzhou, China.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Deng
authors.affiliation: The Biological Therapy Center, The Third Affiliated Hospital, Guangzhou, China.|Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Guangzhou, China.|Department of Anatomy, Zhongshan School of Medicine, Guangzhou, China.
authors.forename: Mei Hua
authors.initials: MH
authors.lastname: Jiang
authors.affiliation: The Biological Therapy Center, The Third Affiliated Hospital, Guangzhou, China.|Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Guangzhou, China.|Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Andy Peng
authors.initials: AP
authors.lastname: Xiang
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D000066673:Cell Self Renewal; D002469:Cell Separation; D004195:Disease Models, Animal; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D039564:Integrin alphaV / Q000378:metabolism*; D007985:Leydig Cells / Q000166:cytology*; D008297:Male; D008698:Mesylates; D008810:Mice, Inbred C57BL; D009929:Organ Size; D017207:Rats, Sprague-Dawley; D013091:Spermatogenesis; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*; D013737:Testis / Q000166:cytology; D013739:Testosterone / Q000172:deficiency*
chemical_list: D015415:Biomarkers; D039564:Integrin alphaV; D008698:Mesylates; D013739:Testosterone; C002994:ethylene dimethanesulfonate
keywords: CD51; Hypogonadism; Stem Leydig cells; Stem cell transplantation; Testosterone