Evidence map›Paper›PMID 41791726›Full record

ArticleStem cells translational medicine2026

Senescence profiling and biomarker identification in cell product based on adipose tissue-derived mesenchymal stromal cells.

Ellen Mønsted Johansen, Cecilie Hoeeg, Rebekka Harary Søndergaard, Lisbeth Drozd Højgaard, Laura Lykke Lethager, Stine Bangsgaard, Jens Kastrup, Tu Hu, Thomas Litman, Morten Juhl Nørgaard

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Article in Stem cells translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Ellen Mønsted JohansenCardiology Stem Cell Centre, The Heart Centre, University Hospital of Copenhagen Rigshospitalet, Copenhagen 2100, Denmark.ORCID 0000-0001-8300-4100
Cecilie HoeegCardiology Stem Cell Centre, The Heart Centre, University Hospital of Copenhagen Rigshospitalet, Copenhagen 2100, Denmark.
Rebekka Harary SøndergaardCardiology Stem Cell Centre, The Heart Centre, University Hospital of Copenhagen Rigshospitalet, Copenhagen 2100, Denmark.
Lisbeth Drozd HøjgaardCardiology Stem Cell Centre, The Heart Centre, University Hospital of Copenhagen Rigshospitalet, Copenhagen 2100, Denmark.
Laura Lykke LethagerCardiology Stem Cell Centre, The Heart Centre, University Hospital of Copenhagen Rigshospitalet, Copenhagen 2100, Denmark.
Stine BangsgaardCardiology Stem Cell Centre, The Heart Centre, University Hospital of Copenhagen Rigshospitalet, Copenhagen 2100, Denmark.
Jens KastrupCardiology Stem Cell Centre, The Heart Centre, University Hospital of Copenhagen Rigshospitalet, Copenhagen 2100, Denmark.
Tu HuTrue Signal, Copenhagen 2300, Denmark.
Thomas LitmanDepartment of Immunology and Microbiology, University of Copenhagen, Copenhagen 2200, Denmark.
Morten Juhl NørgaardCardiology Stem Cell Centre, The Heart Centre, University Hospital of Copenhagen Rigshospitalet, Copenhagen 2100, Denmark.

Funding

Innovation Fund Denmark 0176-00012A
6 · The paper itself

Abstract

BACKGROUND/

aimAdipose tissue-derived mesenchymal stromal cells (ASC) are used in advanced therapy medicinal products due to their regenerative and immunomodulatory properties. Increasing the number of dosages derived from each donor product is essential to reduce variability and improve scalability of cell therapy. However, extended in vitro expansion may induce cellular senescence, potentially compromising therapeutic efficacy. This study aimed to assess the remaining proliferative potential of a cryopreserved ASC product and identify robust transcriptomic -biomarkers of senescence.

methodsASC from five donors were cultured until replicative senescence or passage 10. Morphology, growth kinetics, and confluence were monitored. Bulk RNA sequencing was performed on samples from passage 1, 3, 6, and final passage. Principal component analysis, differential expression, gene set variation analysis, and variance partitioning were used to characterize transcriptional changes and identify biomarkers.

resultsASC maintained stable proliferation and morphology for at least three passages post-thaw. Major transcriptional shifts occurred between passage 3 and later passages. Senescence-associated gene enrichment increased progressively, with donor-specific variation evident at intermediate passages. Forty biomarkers (20 upregulated, 20 downregulated) were identified with expression changes primarily attributable to passage rather than donor identity.

conclusionCryopreserved ASC retain substantial proliferative capacity post-thaw. Senescence develops gradually and is detectable through consistent transcriptomic changes. These findings relate to proliferative and senescence-associated molecular changes and do not directly assess therapeutic efficacy. The identified biomarkers provide a foundation for developing senescence-focused quality control assays to support safe and effective ASC-based therapies.Significance statementThis study identifies promising biomarker candidates for developing a quality control assay to detect cellular senescence and evaluates the remaining replicative potential of a GMP-approved investigational medicinal product. These findings contribute to improving the safety and consistency of cell-based therapies by enabling detection of senescence-related changes.

Indexed as

Adipose TissueBiomarkersCellular SenescenceMesenchymal Stem CellsCell ProliferationCells, CulturedCryopreservationHumansBiomarkersadipose tissue–derived mesenchymal stromal cellsbiomarkerscell therapygene expressionquality controlsenescence

Identifiers

PMID41791726
PMCPMC12965767

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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.