ArticlePloS one2011
Epigenetic dysregulation in mesenchymal stem cell aging and spontaneous differentiation.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers.
What it found
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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.
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Who cites it
111 citing papers in PubMed, 229 citations in OpenAlex.
- Human mesenchymal stem cells derived from limb bud can differentiate into all three embryonic germ layers lineages.Cellular reprogramming · 2012Trial
- Compartment-specific eccDNA patterns reveal senescence associated biomarkers in hUC-MSCs.Scientific reports · 2026Article
- Canine Endometrial Mesenchymal Stem Cells: Characterization and Functional Assessment for Cartilage Repair.International journal of molecular sciences · 2025Article
- Advantages of cell proliferation and immune regulation in CD146+NESTIN+ HUMSCs: insights from single-cell RNA sequencing.Stem cells (Dayton, Ohio) · 2025Article
- Confined Migration Drives Stem Cell Differentiation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Preventing MSC aging and enhancing immunomodulation: Novel strategies for cell-based therapies.Regenerative therapy · 2025Review
- Metabolic Rewiring and Post-Translational Modifications: Unlocking the Mechanisms of Bone Turnover in Osteoporosis.Aging and disease · 2025Review
- Epigenetic mechanisms in stem cell therapies for achilles tendinopathy.Frontiers in cell and developmental biology · 2025Review
- 3D spheroid culture synchronizes heterogeneous MSCs into an immunomodulatory phenotype with enhanced anti-inflammatory effects.iScience · 2024Article
- Therapeutic efficacy and in vivo distribution of human umbilical cord-derived mesenchymal stem cell spheroids transplanted via B-Ultrasound-guided percutaneous portal vein puncture in rhesus monkey models of liver fibrosis.Stem cell research & therapy · 2024Article
- A Mesenchymal stem cell Aging Framework, from Mechanisms to Strategies.Stem cell reviews and reports · 2024Review
- Oxaloacetate as new inducer for osteogenic differentiation of human adipose tissue-derived mesenchymal stem cells in vitro.Molecular biology reports · 2024Article
- Single‑cell sequencing, genetics, and epigenetics reveal mesenchymal stem cell senescence in osteoarthritis (Review).International journal of molecular medicine · 2024Review
- Evaluation of the Composite Skin Patch Loaded with Bioactive Functional Factors Derived from Multicellular Spheres of EMSCs for Regeneration of Full-thickness Skin Defects in Rats.Current stem cell research & therapy · 2024Article
- Epigenetic regulation of mesenchymal stem cell aging through histone modifications.Genes & diseases · 2023Review
- Regulation of self-renewal and senescence in primitive mesenchymal stem cells by Wnt and TGFβ signaling.Stem cell research & therapy · 2023Article
- Comparison of Biological Characteristics of Human Umbilical Cord Wharton's Jelly-Derived Mesenchymal Stem Cells from Extremely Preterm and Term Infants.Tissue engineering and regenerative medicine · 2023Article
- Article
- Impact of Environmental and Epigenetic Changes on Mesenchymal Stem Cells during Aging.International journal of molecular sciences · 2023Review
- [Biological characteristics of sheep peripheral blood mesenchymal stem cell].Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2022Article
51 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
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMesenchymal stem cells (MSCs) hold great promise for the treatment of difficult diseases. As MSCs represent a rare cell population, ex vivo expansion of MSCs is indispensable to obtain sufficient amounts of cells for therapies and tissue engineering. However, spontaneous differentiation and aging of MSCs occur during expansion and the molecular mechanisms involved have been poorly understood. METHODOLOGY/PRINCIPAL
findingsHuman MSCs in early and late passages were examined for their expression of genes involved in osteogenesis to determine their spontaneous differentiation towards osteoblasts in vitro, and of genes involved in self-renewal and proliferation for multipotent differentiation potential. In parallel, promoter DNA methylation and hostone H3 acetylation levels were determined. We found that MSCs underwent aging and spontaneous osteogenic differentiation upon regular culture expansion, with progressive downregulation of TERT and upregulation of osteogenic genes such as Runx2 and ALP. Meanwhile, the expression of genes associated with stem cell self-renewal such as Oct4 and Sox2 declined markedly. Notably, the altered expression of these genes were closely associated with epigenetic dysregulation of histone H3 acetylation in K9 and K14, but not with methylation of CpG islands in the promoter regions of most of these genes. bFGF promoted MSC proliferation and suppressed its spontaneous osteogenic differentiation, with corresponding changes in histone H3 acetylation in TERT, Oct4, Sox2, Runx2 and ALP genes. CONCLUSIONS/SIGNIFICANCE: Our results indicate that histone H3 acetylation, which can be modulated by extrinsic signals, plays a key role in regulating MSC aging and differentiation.
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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.