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DOI | 10.1002/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
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ISSN | 2157-6564 |
EISSN | 2157-6580 |
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 |
推荐引用方式 GB/T 7714 | 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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