Arid
DOI10.1002/sctm.18-0069
Subcutaneous Leydig Stem Cell Autograft: A Promising Strategy to Increase Serum Testosterone
Arora, Himanshu1,2; Zuttion, Marilia Sanches Santos Rizzo2; Nahar, Bruno1; Lamb, Dolores3; Hare, Joshua M.2; Ramasamy, Ranjith1,2
通讯作者Ramasamy, Ranjith
来源期刊STEM CELLS TRANSLATIONAL MEDICINE
ISSN2157-6564
EISSN2157-6580
出版年2019
卷号8期号:1页码:58-65
英文摘要Exogenous testosterone therapy can be used to treat testosterone deficiency; however, it has several adverse effects including infertility due to negative feedback on the hypothalamic-pituitary-gonadal (HPG) axis. Leydig stem cell (LSC) transplantation could provide a new strategy for treating testosterone deficiency, but clinical translatability of injecting stem cells inside the testis is not feasible. Here, we explore the feasibility of subcutaneously autografting LSCs in combination with Sertoli and myoid cells to increase testosterone. We also studied whether the grafted LSCs can be regulated by the HPG axis and the molecular mechanism behind this regulation. LSCs were isolated from the testes of 12-week-old C57BL/6 mice, and subcutaneously autografted in combination with Sertoli cells and myoid cells. We found that LSCs alone were incapable of self-renewal and differentiation. However, in combination with Sertoli cells and myoid cells, LSCs underwent self-renewal as well as differentiation into mature Leydig cells. As a result, the recipient mice that received the LSC autograft showed testosterone production with preserved luteinizing hormone. We found that testosterone production from the autograft was regulated by hedgehog (HH) signaling. Gain of function and loss of function study confirmed that Desert HH (DHH) agonist increased and DHH antagonist decreased testosterone production from autograft. This study is the first to demonstrate that LSCs, when autografted subcutaneously in combination with Sertoli cells and myoid cells, can increase testosterone production. Therefore, LSC autograft may provide a new treatment for testosterone deficiency while simultaneously preserving the HPG axis. Stem Cells Translational Medicine 2019;8:58-65
英文关键词Leydig cell Hypogonadism Fertility Sertoli cell Myoid cell
类型Article
语种英语
国家USA
开放获取类型Green Published, gold
收录类别SCI-E
WOS记录号WOS:000454598900008
WOS关键词DIFFERENTIATION ; TRANSPLANTATION ; SPERMATOGENESIS ; IDENTIFICATION ; PROLIFERATION ; MICE
WOS类目Cell & Tissue Engineering
WOS研究方向Cell Biology
资源类型期刊论文
条目标识符http://119.78.100.177/qdio/handle/2XILL650/218936
作者单位1.Univ Miami, Miller Sch Med, Dept Urol, Miami, FL 33136 USA;
2.Univ Miami, Miller Sch Med, Interdisciplinary Stem Cell Inst, Miami, FL 33136 USA;
3.Weill Cornell Med, Dept Urol, New York, NY USA
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Arora, Himanshu,Zuttion, Marilia Sanches Santos Rizzo,Nahar, Bruno,et al. Subcutaneous Leydig Stem Cell Autograft: A Promising Strategy to Increase Serum Testosterone[J],2019,8(1):58-65.
APA Arora, Himanshu,Zuttion, Marilia Sanches Santos Rizzo,Nahar, Bruno,Lamb, Dolores,Hare, Joshua M.,&Ramasamy, Ranjith.(2019).Subcutaneous Leydig Stem Cell Autograft: A Promising Strategy to Increase Serum Testosterone.STEM CELLS TRANSLATIONAL MEDICINE,8(1),58-65.
MLA Arora, Himanshu,et al."Subcutaneous Leydig Stem Cell Autograft: A Promising Strategy to Increase Serum Testosterone".STEM CELLS TRANSLATIONAL MEDICINE 8.1(2019):58-65.
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