Evidence map›Paper›PMID 28439079›Full record

ArticleScientific reports2017

Translation, but not transfection limits clinically relevant, exogenous mRNA based induction of alpha-4 integrin expression on human mesenchymal stem cells.

Adam Nowakowski, Anna Andrzejewska, Johannes Boltze, Franziska Nitzsche, Li-Li Cui, Jukka Jolkkonen, Piotr Walczak, Barbara Lukomska, Miroslaw Janowski

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.2field-weighted citation impact, top 12% 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

18 citing papers in PubMed, 33 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Proteomic Analysis Reveals Molecular Differences in the Development of Gastric Cancer.Evidence-based complementary and alternative medicine : eCAM · 2022
    Article
  5. Review
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  7. Enhancing the Therapeutic Potential ofInternational journal of molecular sciences · 2020
    Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Single-cell, high-throughput analysis of cell docking to vessel wall.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2019
    Article
  13. Article
  14. Review
  15. Article
  16. Article
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  18. Review
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

9 authors at 5 institutions in 4 countries.

Adam NowakowskiNeuroRepair Department, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
Anna AndrzejewskaNeuroRepair Department, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
Johannes BoltzeFraunhofer-Institute for Cell Therapy and Immunology, Department of Cell Therapy, University of Leipzig, Leipzig, Germany.
Franziska NitzscheFraunhofer-Institute for Cell Therapy and Immunology, Department of Cell Therapy, University of Leipzig, Leipzig, Germany.
Li-Li CuiStroke Recovery Laboratory, Institute of Clinical Medicine - Neurology, University of Eastern Finland, Kuopio, Finland.
Jukka JolkkonenStroke Recovery Laboratory, Institute of Clinical Medicine - Neurology, University of Eastern Finland, Kuopio, Finland.
Piotr WalczakRussell H. Morgan Dept. of Radiology and Radiological Science, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, USA.
Barbara LukomskaNeuroRepair Department, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
Miroslaw JanowskiNeuroRepair Department, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland. mjanows1@jhmi.edu.
Polish Academy of Sciences · PLUniversity of Eastern Finland · FIFraunhofer Institute for Cell Therapy and Immunology · DEUniversity of Lübeck · DEUniversity of Warmia and Mazury in Olsztyn · PL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Mesenchymal stem cells (MSCs) represent promising resource of cells for regenerative medicine in neurological disorders. However, efficient and minimally invasive methods of MSCs delivery to the brain still have to be developed. Intra-arterial route is very promising, but MSCs are missing machinery for diapedesis through blood-brain barrier. Thus, here we have tested a mRNA-based method to induce transient expression of ITGA4, an adhesion molecule actively involved in cell extravasation. We observed that transfection with an ITGA4-mRNA construct bearing a conventional cap analogue (7-methylguanosine) failed to produce ITGA4 protein, but exogenous ITGA4-mRNA was detected in transfected MSCs. This indicates that not transfection, but rather translation being the major roadblock. Stabilization of ITGA4-mRNA with SSB proteins resulted in ITGA4 protein synthesis in HEK293 cells only, whereas in MSCs, satisfactory results were obtained only after using an anti-reverse-cap-analogue (ARCA). The presence of ITGA4 protein in MSCs was transient and lasted for up to 24 h after transfection. Membranous location was confirmed by flow cytometry of viable non-permeabilized cells using anti-ITGA4 antibody. The mRNA-based expression of itga4 transgene is potentially sufficient for diapedesis after intra-arterial delivery. To conclude, mRNA-based engineering of stem cells is a rapid and integration-free method and attractive from the perspective of potential future clinical application.

Indexed as

Gene ExpressionProtein BiosynthesisTransfectionCells, CulturedHumansIntegrin alpha4Membrane ProteinsMesenchymal Stem CellsRNA, MessengerIntegrin alpha4Membrane ProteinsRNA, Messenger

Identifiers

PMID28439079
PMCPMC5430815
OpenAlexW2607206378

What OpenQuestion holds

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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.