ArticleCell death & disease2019
Differentiation of human induced pluripotent stem cells into Leydig-like cells with molecular compounds.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 38 citations in OpenAlex.
- Post-translational modification of proteins in the human testis development pathway.Human reproduction update · 2026Review
- Endocrinology at a Miniature Level: Pluripotent Stem-Cell-Derived Organoid Models of Hypothalamus-Pituitary Axes.Biomolecules · 2026Review
- The emergence of multiple testicular cell lineages in human stem cell-derived testis-like organoids.Development (Cambridge, England) · 2026Article
- In vitro models of the male reproductive system: applications for developmental and reproductive toxicology.Toxicological sciences : an official journal of the Society of Toxicology · 2025Review
- The effects of testicular aging on Leydig cells and the application of stem cells in restoring Leydig cells function.Reproductive biology and endocrinology : RB&E · 2025Review
- Efficient differentiation of human iPSCs into Leydig-like cells capable of long-term stable secretion of testosterone.Stem cell reports · 2025Article
- Review
- Small Molecule Cocktails Promote Fibroblast-to-Leydig-like Cell Conversion for Hypogonadism Therapy.Pharmaceutics · 2023Article
- Advances of three-dimensional (3D) culture systems for in vitro spermatogenesis.Stem cell research & therapy · 2023Review
- In Vitro Differentiation of Leydig Cells From hiPSCs: A First Step Towards a Cellular Therapy for Hypogonadism?Endocrinology · 2022Article
- Rapid Differentiation of Human Embryonic Stem Cells into Testosterone-Producing Leydig Cell-Like Cells In vitro.Tissue engineering and regenerative medicine · 2021Article
- Advances in stem cell research for the treatment of primary hypogonadism.Nature reviews. Urology · 2021Review
- Heading towards a dead end: The role of DND1 in germ line differentiation of human iPSCs.PloS one · 2021Article
- An In Vitro Differentiation Protocol for Human Embryonic Bipotential Gonad and Testis Cell Development.Stem cell reports · 2020Article
- Stem cell-based therapies for fertility preservation in males: Current status and future prospects.World journal of stem cells · 2020Review
- Stem Leydig Cells in the Adult Testis: Characterization, Regulation and Potential Applications.Endocrine reviews · 2020Review
- Generation of Leydig-like cells: approaches, characterization, and challenges.Asian journal of andrologyReview
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Leydig cells (LCs) play crucial roles in producing testosterone, which is critical in the regulation of male reproduction and development. Low levels of testosterone will lead to male hypogonadism. LC transplantation is a promising alternative therapy for male hypogonadism. However, the source of LCs limits this strategy for clinical applications. Thus far, others have reported that LCs can be derived from stem cells by gene transfection, but the safe and effective induction method has not yet been reported. Here, we report that Leydig-like cells can be derived from human induced pluripotent stem cells (iPSCs) using a novel differentiation protocol based on molecular compounds. The iPSCs-derived Leydig-like cells (iPSC-LCs) acquired testosterone synthesis capabilities, had the similar gene expression profiles with LCs, and positively expressed Leydig cell lineage-specific protein markers LHCGR, STAR, SCARB1, SF-1, CYP11A1, HSD3B1, and HSD17B3 as well as negatively expressed iPSC-specific markers NANOG, OCT4, and SOX2. When iPSC-LCs labeled with lipophilic red dye (PKH26) were transplanted into rat testes that were selectively eliminated endogenous LCs using EDS (75 mg/kg), the transplanted iPSC-LCs could survive and function in the interstitium of testes, and accelerate the recovery of serum testosterone levels and testis weights. Collectively, these findings demonstrated that the iPSCs were able to be differentiated into Leydig-like cells by few defined molecular compounds, which may lay the safer groundwork for further clinical application of iPSC-LCs for hypogonadism.
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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.