Evidence map›Paper›PMID 28842435›Full record

ArticlePhysiological genomics2017

Mesenchymal stem cells correct impaired diabetic wound healing by decreasing ECM proteolysis.

Junwang Xu, Carlos Zgheib, Maggie M Hodges, Robert C Caskey, Junyi Hu, Kenneth W Liechty

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PubMed Full text at PMC Publisher
In one paragraph

Article in Physiological genomics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

24 citing papers in PubMed, 1 synthesis or guideline pooled it.

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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

6 authors.

Junwang XuLaboratory for Fetal and Regenerative Biology, University of Colorado Denver - Anschutz Medical Campus, University of Colorado School of Medicine, Aurora, Colorado.
Carlos ZgheibLaboratory for Fetal and Regenerative Biology, University of Colorado Denver - Anschutz Medical Campus, University of Colorado School of Medicine, Aurora, Colorado.
Maggie M HodgesLaboratory for Fetal and Regenerative Biology, University of Colorado Denver - Anschutz Medical Campus, University of Colorado School of Medicine, Aurora, Colorado.
Robert C CaskeyDepartment of Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
Junyi HuLaboratory for Fetal and Regenerative Biology, University of Colorado Denver - Anschutz Medical Campus, University of Colorado School of Medicine, Aurora, Colorado.
Kenneth W LiechtyLaboratory for Fetal and Regenerative Biology, University of Colorado Denver - Anschutz Medical Campus, University of Colorado School of Medicine, Aurora, Colorado; Ken.liechty@childrenscolorado.org.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Impaired diabetic wound healing is associated with a dermal extracellular matrix protein profile favoring proteolysis; within the healing diabetic wound, this is represented by an increase in activated matrix metalloproteinase (MMPs). Treatment of diabetic wounds with mesenchymal stem cells (MSCs) has been shown to improve wound healing; however, there has not yet been an assessment of their ability to correct dysregulation of MMPs in diabetic wounds. Furthermore, there has been no prior assessment of the role of microRNA29b (miR-29b), an inhibitory regulatory molecule that targets MMP-9 mRNA. Using in vitro models of fibroblast coculture with MSCs and in vivo murine wound healing models, we tested the hypothesis that MSCs correct dysregulation of MMPs in a microRNA-29b-dependent mechanism. In this study, we first demonstrated that collagen I and III protein content is significantly reduced in diabetic wounds, and treatment with MSCs significantly improves collagen I content in both nondiabetic and diabetic wounds. We then found that MMP-9 gene expression and protein content were significantly upregulated in diabetic wounds, indicating elevated proteolysis. Treatment with MSCs resulted in a decrease in MMP-9 gene expression and protein content level in diabetic wounds 3 and 7 days after wounding. Zymographic analysis indicated that MSC treatment also decreased the amount of activated MMP-9 present in diabetic wounds. Furthermore, miR-29b expression was inversely associated with MMP-9 gene expression; miR-29b expression was decreased in diabetic wounds and diabetic fibroblast. Following treatment of diabetic wounds with MSCs, as well as in diabetic fibroblasts cocultured with MSCs, miR-29b was significantly increased. These findings suggest a potential mechanism through which MSCs enhance diabetic wound healing by improving collagen I content in diabetic wounds through decreasing MMP-9 expression and increasing miR-29b expression.

Indexed as

AnimalsCoculture TechniquesCollagen Type ICollagen Type IIIDiabetes Mellitus, ExperimentalExtracellular Matrix ProteinsFemaleFibroblastsGene Expression RegulationMatrix Metalloproteinase 9Mesenchymal Stem CellsMesenchymal Stem Cell TransplantationMice, TransgenicMicroRNAsProteolysisWound HealingCollagen Type ICollagen Type IIIExtracellular Matrix ProteinsMatrix Metalloproteinase 9MicroRNAsMIRN29 microRNA, mouseMmp9 protein, mousediabetesextracellular matrixmesenchymal stem cellsproteolysiswound healing

Identifiers

PMID28842435
PMCPMC5668649

What OpenQuestion holds

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Registered trials

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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.