Evidence map›Paper›PMID 26762640›Full record

ArticleStem cell research & therapy2016

PSA-NCAM positive neural progenitors stably expressing BDNF promote functional recovery in a mouse model of spinal cord injury.

Jennifer Butenschön, Tina Zimmermann, Nikolai Schmarowski, Robert Nitsch, Barbara Fackelmeier, Kevin Friedemann, Konstantin Radyushkin, Jan Baumgart, Beat Lutz, Julia Leschik

Open access · goldAbstract read
In one paragraph

Article in Stem cell research & therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.3field-weighted citation impact, top 23% 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

17 citing papers in PubMed, 26 citations in OpenAlex.

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  12. Therapeutic Plasticity of Neural Stem Cells.Frontiers in neurology · 2020
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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

10 authors at 2 institutions in 1 country.

Jennifer ButenschönInstitute of Physiological Chemistry, University Medical Center, Johannes Gutenberg University, Duesbergweg 6, 55128, Mainz, Germany. jwerne01@students.uni-mainz.de.
Tina ZimmermannInstitute of Physiological Chemistry, University Medical Center, Johannes Gutenberg University, Duesbergweg 6, 55128, Mainz, Germany. tina.zimmermann@uni-mainz.de.
Nikolai SchmarowskiInstitute of Microscopic Anatomy and Neurobiology, University Medical Center, Johannes Gutenberg University, Langenbeckstrasse 1, 55131, Mainz, Germany. nikolai.schmarowski@unimedizin-mainz.de.
Robert NitschInstitute of Microscopic Anatomy and Neurobiology, University Medical Center, Johannes Gutenberg University, Langenbeckstrasse 1, 55131, Mainz, Germany. robert.nitsch@uni-mainz.de.
Barbara FackelmeierInstitute of Physiological Chemistry, University Medical Center, Johannes Gutenberg University, Duesbergweg 6, 55128, Mainz, Germany. barbsfa@googlemail.com.
Kevin FriedemannInstitute of Physiological Chemistry, University Medical Center, Johannes Gutenberg University, Duesbergweg 6, 55128, Mainz, Germany. kfriedem@uni-mainz.de.
Konstantin RadyushkinMouse Behavior Outcome Unit, Focus Program Translational Neurosciences (FTN), Johannes Gutenberg University, Hanns-Dieter-Hüsch-Weg 19, 55128, Mainz, Germany. radyushkin@uni-mainz.de.
Jan BaumgartInstitute of Microscopic Anatomy and Neurobiology, University Medical Center, Johannes Gutenberg University, Langenbeckstrasse 1, 55131, Mainz, Germany. jan.baumgart@unimedizin-mainz.de.
Beat LutzInstitute of Physiological Chemistry, University Medical Center, Johannes Gutenberg University, Duesbergweg 6, 55128, Mainz, Germany. blutz@uni-mainz.de.
Julia LeschikInstitute of Physiological Chemistry, University Medical Center, Johannes Gutenberg University, Duesbergweg 6, 55128, Mainz, Germany. leschik@uni-mainz.de.
Johannes Gutenberg University Mainz · DEUniversity Medical Center of the Johannes Gutenberg University Mainz · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundNeural stem cells for the treatment of spinal cord injury (SCI) are of particular interest for future therapeutic use. However, until now, stem cell therapies are often limited due to the inhibitory environment following the injury. Therefore, in this study, we aimed at testing a combinatorial approach with BDNF (brain-derived neurotrophic factor) overexpressing early neural progenitors derived from mouse embryonic stem cells. BDNF is a neurotrophin, which both facilitates neural differentiation of stem cells and favors regeneration of damaged axons.

methodsMouse embryonic stem cells, modified to stably express BDNF-GFP, were differentiated into PSA-NCAM positive progenitors, which were enriched, and SSEA1 depleted by a sequential procedure of magnetic-activated and fluorescence-activated cell sorting. Purified cells were injected into the lesion core seven days after contusion injury of the spinal cord in mice, and the Basso mouse scale (BMS) test to evaluate motor function was performed for 5 weeks after transplantation. To analyze axonal regeneration the anterograde tracer biotinylated dextran amine was injected into the sensorimotor cortex two weeks prior to tissue analysis. Cellular differentiation was analyzed by immunohistochemistry of spinal cord sections.

resultsMotor function was significantly improved in animals obtaining transplanted BDNF-GFP-overexpressing cells as compared to GFP-expressing cells and vehicle controls. Stem cell differentiation in vivo revealed an increase of neuronal and oligodendrocytic lineage differentiation by BDNF as evaluated by immunohistochemistry of the neuronal marker MAP2 (microtubule associated protein 2) and the oligodendrocytic markers ASPA (aspartoacylase) and Olig2 (oligodendrocyte transcription factor 2). Furthermore, axonal tracing showed a significant increase of biotin dextran amine positive corticospinal tract fibers in BDNF-GFP-cell transplanted animals caudally to the lesion site.

conclusionsThe combinatorial therapy approach by transplanting BDNF-overexpressing neural progenitors improved motor function in a mouse contusion model of SCI. Histologically, we observed enhanced neuronal and oligodendrocytic differentiation of progenitors as well as enhanced axonal regeneration.

Indexed as

AnimalsAxonsBrain-Derived Neurotrophic FactorCell DifferentiationCells, CulturedMaleMiceMice, Inbred C57BLMouse Embryonic Stem CellsNeural Cell Adhesion Molecule L1Neural Stem CellsNociceptionRecovery of FunctionSialic AcidsSpinal CordSpinal Cord InjuriesBrain-Derived Neurotrophic FactorNeural Cell Adhesion Molecule L1polysialyl neural cell adhesion moleculeSialic Acids

Identifiers

PMID26762640
PMCPMC4712602
OpenAlexW2234328577

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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.