ArticleAntioxidants & redox signaling2013
H2O2 accumulation mediates differentiation capacity alteration, but not proliferative decline, in senescent human fetal mesenchymal stem cells.
Article in Antioxidants & redox signaling, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed.
- Three-dimensional (3D) culture-primed placental mesenchymal stem cells decrease cellular heterogeneity, significantly enhancing osteogenesis via improving mitochondrial function.Materials today. Bio · 2026Article
- Excess glucose alone depress young mesenchymal stromal/stem cell osteogenesis and mitochondria activity within hours/days via NADJournal of biomedical science · 2024Article
- Mesenchymal Stem Cells and Exosomes: A Novel Therapeutic Approach for Corneal Diseases.International journal of molecular sciences · 2023Review
- Mesenchymal Stem Cell-Based Therapy as a New Approach for the Treatment of Systemic Sclerosis.Clinical reviews in allergy & immunology · 2023Review
- Impact of exogenous hydrogen peroxide on osteogenic differentiation of broiler chicken compact bones derived mesenchymal stem cells.Frontiers in physiology · 2023Article
- Melatonin Improves the Resistance of Oxidative Stress-Induced Cellular Senescence in Osteoporotic Bone Marrow Mesenchymal Stem Cells.Oxidative medicine and cellular longevity · 2022Article
- Advances in mesenchymal stem cell therapy for immune and inflammatory diseases: Use of cell-free products and human pluripotent stem cell-derived mesenchymal stem cells.Stem cells translational medicine · 2021Review
- Protocol for human placental mesenchymal stem cell therapy in a murine model of intra-abdominal infection of hypervirulentSTAR protocols · 2021Article
- Genetic modification by overexpression of target gene in mesenchymal stromal cell for treating liver diseases.Journal of molecular medicine (Berlin, Germany) · 2021Review
- Alteration of fatty acid oxidation by increased CPT1A on replicative senescence of placenta-derived mesenchymal stem cells.Stem cell research & therapy · 2020Article
- Melatonin restores the osteoporosis-impaired osteogenic potential of bone marrow mesenchymal stem cells by preserving SIRT1-mediated intracellular antioxidant properties.Free radical biology & medicine · 2020Article
- A Rapid and Highly PredictiveFrontiers in cell and developmental biology · 2020Article
- Melatonin promotes the BMP9-induced osteogenic differentiation of mesenchymal stem cells by activating the AMPK/β-catenin signalling pathway.Stem cell research & therapy · 2019Article
- Current Trends and Future Perspective of Mesenchymal Stem Cells and Exosomes in Corneal Diseases.International journal of molecular sciences · 2019Review
- Production of Mesenchymal Stem Cells Through Stem Cell Reprogramming.International journal of molecular sciences · 2019Review
- A prospect of cell immortalization combined with matrix microenvironmental optimization strategy for tissue engineering and regeneration.Cell & bioscience · 2019Review
- Mechanical stretch induces antioxidant responses and osteogenic differentiation in human mesenchymal stem cells through activation of the AMPK-SIRT1 signaling pathway.Free radical biology & medicine · 2018Article
- Murine Bone Marrow Mesenchymal Stromal Cells Respond Efficiently to Oxidative Stress Despite the Low Level of Heme Oxygenases 1 and 2.Antioxidants & redox signaling · 2018Article
- Spontaneous up-regulation of SIRT1 during osteogenesis contributes to stem cells' resistance to oxidative stress.Journal of cellular biochemistry · 2018Article
- Oxidative stress induces imbalance of adipogenic/osteoblastic lineage commitment in mesenchymal stem cells through decreasing SIRT1 functions.Journal of cellular and molecular medicine · 2018Article
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Authors and funding
5 authors.
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Abstract
aimsMesenchymal stem cells (MSCs) with multilineage differentiation capacity and immunomodulatory properties are novel sources for cell therapy. However, in vitro expansion of these rare somatic stem cells leads to senescence, resulting in declines of differentiation and proliferative capacities. We therefore investigated the mechanisms mediating senescence in human fetal MSCs termed placenta-derived multipotent cells (PDMCs).
resultsLong-term cultured PDMCs underwent senescence, with increased levels of hydrogen peroxide (H2O2; a reactive oxygen species), positive β-galactosidase staining, decreased sirtuin-1 expression, increased p21 expression, and cell cycle arrest at the G0/G1 phase. Senescent PDMCs also showed decreased osteogenic capacity. Mechanistically, increased p21 expression and proliferative decline were not due to elevated H2O2 levels nor mediated by p53. Instead, inhibition of protein kinase C (PKC)-α and -β in senescent PDMCs decreased p21 expression and reversed cell cycle arrest. H2O2 was involved in the alteration of differentiation potential, since scavenging of H2O2 restored expression of c-MAF, an osteogenic and age-sensitive transcription factor, and osteogenic capacity in senescent PDMCs. INNOVATION: Our findings not only show the effects of senescence on MSCs, but also reveal mechanisms involved in mediating decreased proliferation and differentiation capacity. Moreover, targeting increased levels of H2O2 associated with senescence may reverse the decreased osteogenic capacity of senescent MSCs.
conclusionOur study suggests that the two biological consequences of senescence, differentiation alteration, and proliferative decline, in fetal MSCs are distinctly regulated by the H2O2-c-MAF and PKC-p21 pathways, respectively.
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