Evidence map›Paper›PMID 28677769›Full record

ArticleInternational journal of molecular medicine2017

Valproic acid enforces the priming effect of sphingosine-1 phosphate on human mesenchymal stem cells.

Jisun Lim, Seungun Lee, Hyein Ju, Yonghwan Kim, Jinbeom Heo, Hye-Yeon Lee, Kyung-Chul Choi, Jaekyoung Son, Yeon-Mok Oh, In-Gyu Kim and 1 more

Open access · hybridAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.8field-weighted citation impact, top 14% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 30 citations in OpenAlex.

  1. Review
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  4. Extracellular vesicles: emerging therapeutic agents for liver fibrosis.Extracellular vesicles and circulating nucleic acids · 2025
    Review
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  6. Review
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  8. 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 · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 4 institutions in 1 country.

Jisun LimDepartment of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.
Seungun LeeDepartment of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.
Hyein JuDepartment of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.
Yonghwan KimDepartment of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.
Jinbeom HeoDepartment of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.
Hye-Yeon LeeDepartment of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.
Kyung-Chul ChoiDepartment of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.
Jaekyoung SonDepartment of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.
Yeon-Mok OhDepartment of Pulmonary and Critical Care Medicine, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.
In-Gyu KimDepartment of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
Dong-Myung ShinDepartment of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.
Asan Medical Center · KRUlsan College · KRUniversity of Ulsan · KRSeoul National University · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

Cell MovementGene Expression RegulationHumansLysophospholipidsMAP Kinase Signaling SystemMesenchymal Stem CellsMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Proto-Oncogene Proteins c-aktReceptors, CXCR4SphingosineValproic AcidCXCR4 protein, humanLysophospholipidsMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Proto-Oncogene Proteins c-aktReceptors, CXCR4Sphingosinesphingosine 1-phosphateValproic Acid

Identifiers

PMID28677769
PMCPMC5547989
OpenAlexW2728655487

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.