Evidence map›Paper›PMID 41090719›Full record

ArticleCells2025

A Novel Human Stem Cell Culture Model for Severe Traumatic Brain Injury Reflecting Sexual Dimorphism in Heterotopic Ossification.

Jonas Joneleit, Philipp Leimkühler, Tarek Niemann, Matthias Ruwe, Christian Jantos, Dirk Wähnert, Christian Kaltschmidt, Thomas Vordemvenne, Barbara Kaltschmidt

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cells, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

9 authors.

Jonas JoneleitMolecular Neurobiology, Bielefeld University, Universitätsstrasse 25, 33615 Bielefeld, Germany.
Philipp LeimkühlerDepartment of Trauma and Orthopedic Surgery, Protestant Hospital of Bethel Foundation, Campus Bielefeld-Bethel, University Hospital OWL of Bielefeld University, Burgsteig 13, 33617 Bielefeld, Germany.
Tarek NiemannMolecular Neurobiology, Bielefeld University, Universitätsstrasse 25, 33615 Bielefeld, Germany.
Matthias RuweInstitute of Laboratory Medicine and Microbiology, Protestant Hospital of Bethel Foundation, Campus Bielefeld-Bethel, University Hospital OWL of Bielefeld University, Burgsteig 13, 33617 Bielefeld, Germany.
Christian JantosForschungsverbund BioMedizin Bielefeld/OWL FBMB e.V., Maraweg 21, 33617 Bielefeld, Germany.
Dirk WähnertForschungsverbund BioMedizin Bielefeld/OWL FBMB e.V., Maraweg 21, 33617 Bielefeld, Germany.ORCID 0000-0002-2352-7951
Christian KaltschmidtForschungsverbund BioMedizin Bielefeld/OWL FBMB e.V., Maraweg 21, 33617 Bielefeld, Germany.
Thomas VordemvenneForschungsverbund BioMedizin Bielefeld/OWL FBMB e.V., Maraweg 21, 33617 Bielefeld, Germany.
Barbara KaltschmidtMolecular Neurobiology, Bielefeld University, Universitätsstrasse 25, 33615 Bielefeld, Germany.

Funding

Evangelisches Klinikum Bethel internal grant
6 · The paper itself

Abstract

Heterotopic ossification (HO) is a disease characterized by ectopic bone formation, which can occur following severe traumatic brain injury (TBI). However, the underlying mechanisms remain poorly understood. In this study, we established a stem cell model using adipose-derived stem cells (ADSCs) and skeletal stem cells (SSCs) to examine osteogenic factors present in the sera of TBI patients. Incubation of ADSCs and SSCs with osteoinductive medium supplemented with TBI serum significantly enhanced osteogenic differentiation, particularly in male ADSCs and both female and male SSCs, with male SSCs exhibiting the highest osteogenic potential. Furthermore, we identified TGF-β1 as an important factor involved in these osteogenic processes. Elevated levels of TGF-β1 were detected in the serum of male TBI patients 14 days post-injury. Cellular assays revealed a sexual dimorphism in response to TGF-β1 neutralization: osteogenic differentiation in male SSCs was significantly reduced, while no effect was detectable in female SSCs. These findings, together with the rarity of HO in female patients, suggest that TGF-β1 plays a central role in the development of HO in males. Furthermore, this study highlights the importance of considering sex-specific mechanisms in traumatic HO for the development of sex-specific therapy options.

Indexed as

Brain Injuries, TraumaticCell Culture TechniquesModels, BiologicalOssification, HeterotopicSex CharacteristicsStem CellsAdultCell DifferentiationCells, CulturedFemaleHumansMaleMiddle AgedOsteogenesisTransforming Growth Factor beta1Transforming Growth Factor beta1adipose-derived stem cellsheterotopic ossificationosteogenic differentiationS100Bsexual dimorphismskeletal stem cellsTGF-β1traumatic brain injury

Identifiers

PMID41090719
PMCPMC12524128

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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.