ArticleStem cells translational medicine2019
Subcutaneous Leydig Stem Cell Autograft: A Promising Strategy to Increase Serum Testosterone.
Article in Stem cells translational medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
16 citing papers in PubMed, 36 citations in OpenAlex.
- Clinician's guide to the management of azoospermia induced by exogenous testosterone or anabolic-androgenic steroids.Asian journal of andrology · 2025Review
- Efficient differentiation of human iPSCs into Leydig-like cells capable of long-term stable secretion of testosterone.Stem cell reports · 2025Article
- The role of leptin in the male reproductive system.Journal of the Turkish German Gynecological Association · 2024Article
- A narrative review on inflammaging and late-onset hypogonadism.Frontiers in endocrinology · 2024Review
- The role of leptin and low testosterone in obesity.International journal of impotence research · 2022Review
- Leptin secreted from testicular microenvironment modulates hedgehog signaling to augment the endogenous function of Leydig cells.Cell death & disease · 2022Article
- Advances in stem cell research for the treatment of primary hypogonadism.Nature reviews. Urology · 2021Review
- Rapid Differentiation of Human Embryonic Stem Cells into Testosterone-Producing Leydig Cell-Like Cells In vitro.Tissue engineering and regenerative medicine · 2021Article
- Exogenous testosterone replacement therapy versus raising endogenous testosterone levels: current and future prospects.F&S reviews · 2021Article
- Endosialin defines human stem Leydig cells with regenerative potential.Human reproduction (Oxford, England) · 2020Article
- Conversion of Fibroblast into Functional Leydig-like Cell Using Defined Small Molecules.Stem cell reports · 2020Article
- Stem Leydig Cells in the Adult Testis: Characterization, Regulation and Potential Applications.Endocrine reviews · 2020Review
- Restorative functions of Autologous Stem Leydig Cell transplantation in a Testosterone-deficient non-human primate model.Theranostics · 2020Article
- Directing differentiation of human induced pluripotent stem cells toward androgen-producing Leydig cells rather than adrenal cells.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Age Induced Nitroso-Redox Imbalance Leads to Subclinical Hypogonadism in Male Mice.Frontiers in endocrinology · 2019Article
- Generation of Leydig-like cells: approaches, characterization, and challenges.Asian journal of andrologyReview
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.