ArticleInternational journal of molecular medicine2017
Valproic acid enforces the priming effect of sphingosine-1 phosphate on human mesenchymal stem cells.
Article in International journal of molecular medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 30 citations in OpenAlex.
- Priming of Mesenchymal Stem Cells for Tendon Regeneration: Mechanisms and Clinical Translation.Stem cell reviews and reports · 2026Review
- Development of mesenchymal stem cells: therapeutic effect and prospect for rheumatoid arthritis.Stem cell research & therapy · 2025Review
- Assessment of the Therapeutic Effectiveness of Glutathione-Enhanced Mesenchymal Stem Cells in Rat Models of Chronic Bladder Ischemia-Induced Overactive Bladder and Detrusor Underactivity.International journal of stem cells · 2025Article
- Extracellular vesicles: emerging therapeutic agents for liver fibrosis.Extracellular vesicles and circulating nucleic acids · 2025Review
- Insulin-Like Growth Factor 2 Secreted from Mesenchymal Stem Cells with High Glutathione Levels Alleviates Osteoarthritis via Paracrine Rejuvenation of Senescent Chondrocytes.Biomaterials research · 2025Article
- How to enhance MSCs therapeutic properties? An insight on potentiation methods.Stem cell research & therapy · 2024Review
- Engineering mesenchymal stem cells for premature ovarian failure: overcoming challenges and innovating therapeutic strategies.Theranostics · 2024Review
- Guarana (Paullinia cupana) as a potential tool for mesenchymal stromal cells priming in regenerative medicine.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2024Article
- Therapeutic Effects of Mesenchymal/Stromal Stem Cells and Their Derived Extracellular Vesicles in Rheumatoid Arthritis.Stem cells translational medicine · 2023Article
- Activating transcription factor-2 supports the antioxidant capacity and ability of human mesenchymal stem cells to prevent asthmatic airway inflammation.Experimental & molecular medicine · 2023Article
- Functional enhancement strategies to potentiate the therapeutic properties of mesenchymal stromal cells for respiratory diseases.Frontiers in pharmacology · 2023Review
- Enhancement strategies for mesenchymal stem cells and related therapies.Stem cell research & therapy · 2022Review
- Small-sized mesenchymal stem cells with high glutathione dynamics show improved therapeutic potency in graft-versus-host disease.Clinical and translational medicine · 2021Article
- Coordinated Regulation of Mesenchymal Stem Cell Migration by Various Chemotactic Stimuli.International journal of molecular sciences · 2020Article
- Therapeutic Efficacy of Human Embryonic Stem Cell-Derived Multipotent Stem/Stromal Cells in Diabetic Detrusor Underactivity: A Preclinical Study.Journal of clinical medicine · 2020Article
- Umbilical Cord-Derived Mesenchymal Stem Cells Are Able to Use bFGF Treatment and Represent a Superb Tool for Immunosuppressive Clinical Applications.International journal of molecular sciences · 2020Article
- Glutathione dynamics determine the therapeutic efficacy of mesenchymal stem cells for graft-versus-host disease via CREB1-NRF2 pathway.Science advances · 2020Article
- Phorbol ester activates human mesenchymal stem cells to inhibit B cells and ameliorate lupus symptoms in MRL.Theranostics · 2020Article
- Control of mesenchymal stem cell biology by histone modifications.Cell & bioscience · 2020Review
- Evaluating the Differential Effects of Valproic Acid on Wharton's Jelly Mesenchymal Stem Cells.Advanced pharmaceutical bulletin · 2019Article
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Engraftment and homing of mesenchymal stem cells (MSCs) are modulated by priming factors including the bioactive lipid sphingosine-1-phosphate (S1P), by stimulating CXCR4 receptor signaling cascades. However, limited in vivo efficacy and the remaining priming molecules prior to administration of MSCs can provoke concerns regarding the efficiency and safety of MSC priming. Here, we showed that valproic acid (VPA), a histone deacetylase inhibitor, enforced the priming effect of S1P at a low dosage for human umbilical cord-derived MSCs (UC-MSCs). A DNA-methylation inhibitor, 5-azacytidine (5-Aza), and VPA increased the expression of CXCR4 in UC-MSCs. In particular, UC-MSCs primed with a suboptimal dose (50 nM) of S1P in combination with 0.5 mM VPA (VPA+S1P priming), but not 1 µM 5-Aza, significantly improved the migration activity in response to stromal cell-derived factor 1 (SDF-1) concomitant with the activation of both MAPKp42/44 and AKT signaling cascades. Both epigenetic regulatory compounds had little influence on cell surface marker phenotypes and the multi-potency of UC-MSCs. In contrast, VPA+S1P priming of UC-MSCs potentiated the proliferation, colony forming unit-fibroblast, and anti-inflammatory activities, which were severely inhibited in the case of 5-Aza treatment. Accordingly, the VPA+S1P-primed UC-MSCs exhibited upregulation of a subset of genes related to stem cell migration and anti-inflammation response. Thus, the present study demonstrated that VPA enables MSC priming with S1P at a low dosage by enhancing their migration and other therapeutic beneficial activities. This priming strategy for MSCs may provide a more efficient and safe application of MSCs for treating a variety of intractable disorders.
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