Evidence map›Paper›PMID 31631568›Full record

ArticleStem cells translational medicine2019

Smurf1 Silencing Using a LNA-ASOs/Lipid Nanoparticle System to Promote Bone Regeneration.

Patricia García-García, Mario Ruiz, Ricardo Reyes, Araceli Delgado, Carmen Évora, José Antonio Riancho, José Carlos Rodríguez-Rey, Flor María Pérez-Campo

Open access · goldAbstract read
In one paragraph

Article in Stem cells translational medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.0field-weighted citation impact, top 24% 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

16 citing papers in PubMed, 21 citations in OpenAlex.

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  8. NEDD4 E3 Ligases: Functions and Mechanisms in Bone and Tooth.International journal of molecular sciences · 2022
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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

8 authors at 2 institutions in 1 country.

Patricia García-GarcíaDepartment of Chemical Engineering and Pharmaceutical Technology, Institute of Biomedical Technologies (ITB), University of La Laguna, La Laguna, Spain.
Mario RuizDepartment of Molecular Biology, Faculty of Medicine, University of Cantabria, IDIVAL, Santander, Spain.
Ricardo ReyesDepartment of Biochemistry, Microbiology, Cellular Biology and Genetics, Institute of Biomedical Technologies (ITB), University of La Laguna, La Laguna, Spain.ORCID 0000-0002-1765-3257
Araceli DelgadoDepartment of Chemical Engineering and Pharmaceutical Technology, Institute of Biomedical Technologies (ITB), University of La Laguna, La Laguna, Spain.
Carmen ÉvoraDepartment of Chemical Engineering and Pharmaceutical Technology, Institute of Biomedical Technologies (ITB), University of La Laguna, La Laguna, Spain.
José Antonio RianchoDepartment of Internal Medicine, Hospital U M Valdecilla, University of Cantabria, IDIVAL, Santander, Spain.
José Carlos Rodríguez-ReyDepartment of Molecular Biology, Faculty of Medicine, University of Cantabria, IDIVAL, Santander, Spain.
Flor María Pérez-CampoDepartment of Molecular Biology, Faculty of Medicine, University of Cantabria, IDIVAL, Santander, Spain.ORCID 0000-0002-9872-7990
Universidad de Cantabria · ESUniversidad de La Laguna · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Despite the great advance of bone tissue engineering in the last few years, repair of bone defects remains a major problem. Low cell engraftment and dose-dependent side effects linked to the concomitant administration of bone morphogenetic proteins (BMPs) are the main problems currently hindering the clinical use of mesenchymal stem cell (MSC)-based therapies in this field. We have managed to bypass these drawbacks by combining the silencing the Smurf1 ubiquitin ligase in MSCs with the use of a scaffold that sustainably releases low doses of BMP-2. In this system, Smurf1 silencing is achieved by using GapmeRs, a clinically safe method that avoids the use of viral vectors, facilitating its translation to the clinic. Here, we show that a single transient transfection with a small quantity of a Smurf1-specific GapmeR is able to induce a significant level of silencing of the target gene, enough to prime MSCs for osteogenic differentiation. Smurf1 silencing highly increases MSCs responsiveness to BMP-2, allowing a dramatic reduction of the dose needed to achieve the desired therapeutic effect. The combination of these primed cells with alginate scaffolds designed to sustainably and locally release low doses of BMP-2 to the defect microenvironment is able to induce the formation of a mature bone matrix both in an osteoporotic rat calvaria system and in a mouse ectopic model. Importantly, this approach also enhances osteogenic differentiation in MSCs from osteoporotic patients, characterized by a reduced bone-forming potential, even at low BMP doses, underscoring the regenerative potential of this system. Stem Cells Translational Medicine 2019;8:1306&1317.

Indexed as

Bone RegenerationAlginatesAnimalsBone Morphogenetic Protein 2Cell DifferentiationCells, CulturedFemaleGene SilencingHumansLipidsMesenchymal Stem CellsNanoparticlesOligonucleotidesOligonucleotides, AntisenseRatsRats, Sprague-DawleyAlginatesBmp2 protein, ratBone Morphogenetic Protein 2Lipidslocked nucleic acidOligonucleotidesOligonucleotides, AntisenseSmurf1 protein, ratUbiquitin-Protein LigasesBMPBone regenerationGapmeRLNA-ASOMesenchymal stem cellsOsteogenesisSmurf1

Identifiers

PMID31631568
PMCPMC6877774
OpenAlexW2981462562

What OpenQuestion holds

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LicenceCC BY-NC
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.