Evidence map›Paper›PMID 39824187›Full record

ArticleStem cell reports2025

Efficient differentiation of human iPSCs into Leydig-like cells capable of long-term stable secretion of testosterone.

Katsuya Sato, Michiyo Koyanagi-Aoi, Keiichiro Uehara, Yosuke Yamashita, Masakazu Shinohara, Suji Lee, Anika Reinhardt, Knut Woltjen, Koji Chiba, Hideaki Miyake and 2 more

Abstract read
In one paragraph

Article in Stem cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

  1. Review
  2. Article
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  4. Article
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  6. NAM journal · 2025
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Katsuya SatoDivision of Stem Cell Medicine, Graduate School of Medicine, Kobe University, Kobe, Japan; Division of Advanced Medical Science, Graduate School of Science, Technology and Innovation, Kobe University, Kobe, Japan; Division of Urology, Graduate School of Medicine, Kobe University, Kobe, Japan.
Michiyo Koyanagi-AoiDivision of Stem Cell Medicine, Graduate School of Medicine, Kobe University, Kobe, Japan; Division of Advanced Medical Science, Graduate School of Science, Technology and Innovation, Kobe University, Kobe, Japan; Center for Human Resource Development for Regenerative Medicine, Kobe University Hospital, Kobe, Japan.
Keiichiro UeharaDivision of Stem Cell Medicine, Graduate School of Medicine, Kobe University, Kobe, Japan; Division of Advanced Medical Science, Graduate School of Science, Technology and Innovation, Kobe University, Kobe, Japan; Department of Diagnostic Pathology, Graduate School of Medicine, Kobe University, Kobe, Japan.
Yosuke YamashitaDivision of Stem Cell Medicine, Graduate School of Medicine, Kobe University, Kobe, Japan; Division of Advanced Medical Science, Graduate School of Science, Technology and Innovation, Kobe University, Kobe, Japan; Division of Urology, Graduate School of Medicine, Kobe University, Kobe, Japan.
Masakazu ShinoharaThe Integrated Center for Mass Spectrometry, Graduate School of Medicine, Kobe University, Kobe, Japan; Division of Molecular Epidemiology, Graduate School of Medicine, Kobe University, Kobe, Japan.
Suji LeeDepartment of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
Anika ReinhardtDepartment of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
Knut WoltjenDepartment of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
Koji ChibaDivision of Urology, Graduate School of Medicine, Kobe University, Kobe, Japan.
Hideaki MiyakeDivision of Urology, Graduate School of Medicine, Kobe University, Kobe, Japan.
Masato FujisawaDivision of Urology, Graduate School of Medicine, Kobe University, Kobe, Japan.
Takashi AoiDivision of Stem Cell Medicine, Graduate School of Medicine, Kobe University, Kobe, Japan; Division of Advanced Medical Science, Graduate School of Science, Technology and Innovation, Kobe University, Kobe, Japan; Center for Human Resource Development for Regenerative Medicine, Kobe University Hospital, Kobe, Japan; Division of Signal Pathways, Biosignal Research Center, Kobe University, Kobe, Japan. Electronic address: takaaoi@med.kobe-u.ac.jp.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Late-onset hypogonadism (LOH) syndrome is characterized by age-related testosterone deficiency and negatively affects the quality of life of older men. A promising therapeutic approach for LOH syndrome is transplantation of testosterone-producing Leydig-like cells (LLCs) derived from human induced pluripotent stem cells (hiPSCs). However, previous studies have encountered obstacles, such as limited cell longevity, insufficient testosterone production, and inefficiency of differentiation. To address these issues, we developed a novel protocol that includes forced NR5A1 expression, a cytokine cocktail promoting mesoderm differentiation, and a transitional shift from 3D to 2D cultures. The resultant cells survived on culture dishes for over 16 weeks, produced 22-fold more testosterone than the conventional method, and constituted a homogeneous population of LLCs with a differentiation efficiency exceeding 99% without purification. Furthermore, these LLCs were successfully engrafted subcutaneously into mice, resulting in increased serum testosterone levels. Our study will facilitate innovative therapeutic strategies for LOH syndrome.

Indexed as

Cell DifferentiationInduced Pluripotent Stem CellsLeydig CellsTestosteroneAnimalsCell Culture TechniquesCells, CulturedHumansHypogonadismMaleMiceTestosteronedifferentiationiPS cellLeydig cellLOH syndrometestosterone

Identifiers

PMID39824187
PMCPMC11864132

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.