ArticleProceedings of the National Academy of Sciences of the United States of America2019
Directing differentiation of human induced pluripotent stem cells toward androgen-producing Leydig cells rather than adrenal cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Why does COVID-19 kill more elderly men than women? Is there a role for testosterone?Andrology · 2021Pooled it
- 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
- 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
- Mechanisms of Leydig Cell Aging and Obesity-Related Hypogonadism in Men: A Review.Medical science monitor : international medical journal of experimental and clinical research · 2025Review
- Mechanical signal-mediated mitochondria-endoplasmic reticulum contacts modulate Leydig cell testosterone biosynthesis during testis development.Molecular human reproduction · 2025Article
- 3D Bioprinted Coaxial Testis Model Using Human Induced Pluripotent Stem Cells:A Step Toward Bicompartmental Cytoarchitecture and Functionalization.Advanced healthcare materials · 2025Article
- Efficient differentiation of human iPSCs into Leydig-like cells capable of long-term stable secretion of testosterone.Stem cell reports · 2025Article
- Review
- Article
- Generation of glucocorticoid-producing cells derived from human pluripotent stem cells.Cell reports methods · 2023Article
- Article
- Reconstitution of human adrenocortical specification and steroidogenesis using induced pluripotent stem cells.Developmental cell · 2022Article
- High-fidelity reprogramming into Leydig-like cells by CRISPR activation and paracrine factors.PNAS nexus · 2022Article
- In Vitro Differentiation of Leydig Cells From hiPSCs: A First Step Towards a Cellular Therapy for Hypogonadism?Endocrinology · 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
- Adrenal cortex renewal in health and disease.Nature reviews. Endocrinology · 2021Review
Corrections and comments
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Reduced serum testosterone (T), or hypogonadism, affects millions of men and is associated with many pathologies, including infertility, cardiovascular diseases, metabolic syndrome, and decreased libido and sexual function. Administering T-replacement therapy (TRT) reverses many of the symptoms associated with low T levels. However, TRT is linked to side effects such as infertility and increased risk of prostate cancer and cardiovascular diseases. Thus, there is a need to obtain T-producing cells that could be used to treat hypogonadism via transplantation and reestablishment of T-producing cell lineages in the body. T is synthesized by Leydig cells (LCs), proposed to derive from mesenchymal cells of mesonephric origin. Although mesenchymal cells have been successfully induced into LCs, the limited source and possible trauma to donors hinders their application to clinical therapies. Alternatively, human induced pluripotent stem cells (hiPSCs), which are expandable in culture and have the potential to differentiate into all somatic cell types, have become the emerging source of autologous cell therapies. We have successfully induced the differentiation of hiPSCs into either human Leydig-like (hLLCs) or adrenal-like cells (hALCs) using chemically defined culture conditions. Factors critical for the development of LCs were added to both culture systems. hLLCs expressed all steroidogenic genes and proteins important for T biosynthesis, synthesized T rather than cortisol, secreted steroid hormones in response to dibutyryl-cAMP and 22(
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