Evidence map›Paper›PMID 33579367›Full record

ArticleStem cell research & therapy2021

Enhanced anti-inflammatory effects of mesenchymal stromal cells mediated by the transient ectopic expression of CXCR4 and IL10.

Rosario Hervás-Salcedo, María Fernández-García, Miriam Hernando-Rodríguez, Oscar Quintana-Bustamante, Jose-Carlos Segovia, Marcio Alvarez-Silva, Mariano García-Arranz, Pablo Minguez, Victoria Del Pozo, Marta Rodríguez de Alba and 5 more

Open access · goldAbstract read
In one paragraph

Article in Stem cell research & therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 1 pooled it
4.1field-weighted citation impact, top 5% 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

28 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.

  1. Association of theGenetics research · 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

15 authors at 4 institutions in 2 countries.

Rosario Hervás-SalcedoHematopoietic Innovative Therapies Division, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Av. Complutense 40, 28040, Madrid, Spain.
María Fernández-GarcíaHematopoietic Innovative Therapies Division, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Av. Complutense 40, 28040, Madrid, Spain.
Miriam Hernando-RodríguezHematopoietic Innovative Therapies Division, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Av. Complutense 40, 28040, Madrid, Spain.
Oscar Quintana-BustamanteHematopoietic Innovative Therapies Division, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Av. Complutense 40, 28040, Madrid, Spain.
Jose-Carlos SegoviaHematopoietic Innovative Therapies Division, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Av. Complutense 40, 28040, Madrid, Spain.
Marcio Alvarez-SilvaStem Cell and Bioengineering Laboratory, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
Mariano García-ArranzInstituto de Investigaciones Sanitarias Fundación Jiménez Díaz (IIS-FJD), Madrid, Spain.
Pablo MinguezCentro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.
Victoria Del PozoInstituto de Investigaciones Sanitarias Fundación Jiménez Díaz (IIS-FJD), Madrid, Spain.
Marta Rodríguez de AlbaInstituto de Investigaciones Sanitarias Fundación Jiménez Díaz (IIS-FJD), Madrid, Spain.
Damián García-OlmoInstituto de Investigaciones Sanitarias Fundación Jiménez Díaz (IIS-FJD), Madrid, Spain.
Carmen AyusoCentro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.
María Luisa LamanaHematopoietic Innovative Therapies Division, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Av. Complutense 40, 28040, Madrid, Spain.
Juan A BuerenHematopoietic Innovative Therapies Division, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Av. Complutense 40, 28040, Madrid, Spain. juan.bueren@ciemat.es.
Rosa María YañezHematopoietic Innovative Therapies Division, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Av. Complutense 40, 28040, Madrid, Spain. rosamaria.yanez@ciemat.es.ORCID 0000-0003-0132-3402
Centre for Biomedical Network Research on Rare Diseases · ESHospital Universitario Fundación Jiménez Díaz · ESCentro de Investigación Biomédica en Red de Enfermedades Respiratorias · ESUniversidade Federal de Santa Catarina · BR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMesenchymal stromal cells (MSCs) constitute one of the cell types most frequently used in cell therapy. Although several studies have shown the efficacy of these cells to modulate inflammation in different animal models, the results obtained in human clinical trials have been more modest. Here, we aimed at improving the therapeutic properties of MSCs by inducing a transient expression of two molecules that could enhance two different properties of these cells. With the purpose of improving MSC migration towards inflamed sites, we induced a transient expression of the C-X-C chemokine receptor type 4 (CXCR4). Additionally, to augment the anti-inflammatory properties of MSCs, a transient expression of the anti-inflammatory cytokine, interleukin 10 (IL10), was also induced.

methodsHuman adipose tissue-derived MSCs were transfected with messenger RNAs carrying the codon-optimized versions of CXCR4 and/or IL10. mRNA-transfected MSCs were then studied, first to evaluate whether the characteristic phenotype of MSCs was modified. Additionally, in vitro and also in vivo studies in an LPS-induced inflamed pad model were conducted to evaluate the impact associated to the transient expression of CXCR4 and/or IL10 in MSCs.

resultsTransfection of MSCs with CXCR4 and/or IL10 mRNAs induced a transient expression of these molecules without modifying the characteristic phenotype of MSCs. In vitro studies then revealed that the ectopic expression of CXCR4 significantly enhanced the migration of MSCs towards SDF-1, while an increased immunosuppression was associated with the ectopic expression of IL10. Finally, in vivo experiments showed that the co-expression of CXCR4 and IL10 increased the homing of MSCs into inflamed pads and induced an enhanced anti-inflammatory effect, compared to wild-type MSCs.

conclusionsOur results demonstrate that the transient co-expression of CXCR4 and IL10 enhances the therapeutic potential of MSCs in a local inflammation mouse model, suggesting that these mRNA-modified cells may constitute a new step in the development of more efficient cell therapies for the treatment of inflammatory diseases.

Indexed as

Mesenchymal Stem CellsAnimalsCell MovementChemokine CXCL12Ectopic Gene ExpressionInterleukin-10Receptors, CXCR4Signal TransductionChemokine CXCL12Interleukin-10Receptors, CXCR4CXCR4IL10InflammationMesenchymal stromal cellsmRNA-modified MSCsMSC homing

Identifiers

PMID33579367
PMCPMC7881581
OpenAlexW3126753747

What OpenQuestion holds

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LicenceCC BY
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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.