ArticleStem cells (Dayton, Ohio)2014
Cell senescence abrogates the therapeutic potential of human mesenchymal stem cells in the lethal endotoxemia model.
Article in Stem cells (Dayton, Ohio), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers, 4 of them syntheses that pooled 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.
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.
Who cites it
118 citing papers in PubMed, 4 syntheses or guidelines pooled it, 194 citations in OpenAlex.
- Rejuvenation of Bone Marrow Mesenchymal Stem Cells: Mechanisms and Their Application in Senile Osteoporosis Treatment.Biomolecules · 2025Pooled it
- Effect of Bone Marrow Mesenchymal Stromal Cell Therapies in Rodent Models of Sepsis: A Meta-Analysis.Frontiers in immunology · 2021Pooled it
- Efficacy of mesenchymal stem cell therapy for sepsis: a meta-analysis of preclinical studies.Stem cell research & therapy · 2020Pooled it
- Pooled it
- Frailty in People with HIV Is Linked to Inflammation, Bone Health, and T-Cell Exhaustion.The Journal of infectious diseases · 2026Article
- Polymer Matrix-Based 3D Culture Significantly Enhances the Differentiation and Immunomodulatory Functions of Human Adipose-Derived Stem Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Therapeutic strategy for exosome-based bone regeneration to osteoporosis: Challenges and potential solutions.Journal of advanced research · 2026Review
- Low-Intensity Electric Field Stimulation Modulates Proliferation, Stemness, and Chondrogenesis of Tonsil-Derived Mesenchymal Stem Cells.Tissue engineering and regenerative medicine · 2026Article
- Hematopoietic (stem) cells-The elixir of life?FEBS letters · 2026Review
- Mesenchymal Stem Cell-derived Exosomes in the Treatment of End-stage Liver Disease.Current stem cell research & therapy · 2026Review
- Comprehensive bulk and single-cell RNA sequencing uncovers senescence-associated biomarkers in therapeutic mesenchymal stem cells.Scientific reports · 2025Article
- FTO Suppresses Dental Pulp Stem Cell Senescence by DestabilizingBiomolecules · 2025Article
- Ontogenetic stage and type of donor cells shape extracellular vesicles' therapeutic potential for osteoarthritis.Stem cell research & therapy · 2025Article
- Mesenchymal Stem Cells with Simultaneous Overexpression of GPX3 and CD47 for the Treatment of Drug-Induced Acute Liver Injury.Veterinary sciences · 2025Article
- Disorganized chromatin hierarchy and stem cell aging in a male patient of atypical laminopathy-based progeria mandibuloacral dysplasia type A.Nature communications · 2024Article
- Leveraging Cell Migration Dynamics to Discriminate Between Senescent and Presenescent Human Mesenchymal Stem Cells.Cellular and molecular bioengineering · 2024Article
- Machine learning reveals the rules governing the efficacy of mesenchymal stromal cells in septic preclinical models.Stem cell research & therapy · 2024Article
- Role of Mesenchymal Stem/Stromal Cells (MSCs) and MSC-Derived Extracellular Vesicles (EVs) in Prevention of Telomere Length Shortening, Cellular Senescence, and Accelerated Biological Aging.Bioengineering (Basel, Switzerland) · 2024Review
- miR-155-5p/Bmal1 Modulates the Senescence and Osteogenic Differentiation of Mouse BMSCs through the Hippo Signaling Pathway.Stem cell reviews and reports · 2024Article
- Research progress on optimization ofFrontiers in bioengineering and biotechnology · 2024Review
58 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Mesenchymal stem cells (MSCs) possess unique paracrine and immunosuppressive properties, which make them useful candidates for cellular therapy. Here, we address how cellular senescence influences the therapeutic potential of human MSCs (hMSCs). Senescence was induced in bone marrow-derived hMSC cultures with gamma irradiation. Control and senescent cells were tested for their immunoregulatory activity in vitro and in vivo, and an extensive molecular characterization of the phenotypic changes induced by senescence was performed. We also compared the gene expression profiles of senescent hMSCs with a collection of hMSCs used in an ongoing clinical study of Graft Versus Host disease (GVHD). Our results show that senescence induces extensive phenotypic changes in hMSCs and abrogates their protective activity in a murine model of LPS-induced lethal endotoxemia. Although senescent hMSCs retain an ability to regulate the inflammatory response on macrophages in vitro, and, in part retain their capacity to significantly inhibit lymphocyte proliferation, they have a severely impaired migratory capacity in response to proinflammatory signals, which is associated with an inhibition of the AP-1 pathway. Additionally, expression analysis identified PLEC, C8orf48, TRPC4, and ZNF14, as differentially regulated genes in senescent hMSCs that were similarly regulated in those hMSCs which failed to produce a therapeutic effect in a GVHD trial. All the observed phenotypic alterations were confirmed in replicative-senescent hMSCs. In conclusion, this study highlights important changes in the immunomodulatory phenotype of senescent hMSCs and provides candidate gene signatures which may be useful to evaluate the therapeutic potential of hMSCs used in future clinical studies.
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Registered trials
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.