ArticleEndocrinology2021
Differentiation of Human Induced Pluripotent Stem Cells Into Testosterone-Producing Leydig-like Cells.
Article in Endocrinology, 2021. 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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Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
- Testicular ageing as a central hallmark of male senescence: characteristics, molecular mechanisms and emerging therapeutic strategies.Annals of medicine · 2026Review
- Post-translational modification of proteins in the human testis development pathway.Human reproduction update · 2026Review
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- The emergence of multiple testicular cell lineages in human stem cell-derived testis-like organoids.Development (Cambridge, England) · 2026Article
- Review
- 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
- Characterization of Steroid Metabolic Pathways in Established Human and Mouse Cell Models.International journal of molecular sciences · 2025Article
- Efficient differentiation of human iPSCs into Leydig-like cells capable of long-term stable secretion of testosterone.Stem cell reports · 2025Article
- Extracellular vesicles in stem cell-based gonadal regeneration: mechanisms, therapeutic potential, and translational challenges.Frontiers in veterinary science · 2025Review
- Review
- A new humanHuman reproduction open · 2025Article
- Enhancing terminal erythroid differentiation in human embryonic stem cells through TRIB3 overexpression.Heliyon · 2024Article
- High-fidelity reprogramming into Leydig-like cells by CRISPR activation and paracrine factors.PNAS nexus · 2022Article
- Emerging concepts on Leydig cell development in fetal and adult testis.Frontiers in endocrinology · 2022Review
- In Vitro Differentiation of Leydig Cells From hiPSCs: A First Step Towards a Cellular Therapy for Hypogonadism?Endocrinology · 2022Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Late-onset hypogonadism (LOH) syndrome, due to a partial lack of testosterone, decreases the quality of life of older men. Testosterone is mainly secreted by Leydig cells in the testes. Leydig cell transplantation is expected to be a promising alternative to conventional testosterone replacement therapy for LOH syndrome. We herein report a simple and robust protocol for directed differentiation of human induced pluripotent stem cells (hiPSCs) into Leydig-like cells by doxycycline-inducible overexpression of NR5A1 and treatment with a combination of 8-bromoadenosine-3',5'-cyclic monophosphate (8-Br-cAMP) and forskolin. The differentiated cells expressed the steroidogenic enzyme genes STAR, CYP11A1, CYP17A1, and HSD3B2 and the specific markers of adult Leydig cells HSD17B3, INSL3, and LHCGR. Furthermore, we confirmed the secretion of functional testosterone from the cells into the culture supernatant by a testosterone-sensitive cell proliferation assay. These findings showed that the hiPSCs were able to be differentiated into Leydig-like cells, supporting the expectation that hiPSC-derived Leydig-like cells can be novel tools for treating LOH syndrome.
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