Evidence map›Paper›PMID 34478241›Full record

ArticleJournal of extracellular vesicles2021

Small extracellular vesicles released by infused mesenchymal stromal cells target M2 macrophages and promote TGF-β upregulation, microvascular stabilization and functional recovery in a rodent model of severe spinal cord injury.

Masahito Nakazaki, Tomonori Morita, Karen L Lankford, Philip W Askenase, Jeffery D Kocsis

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of extracellular vesicles, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
113citing papers in PubMed, 3 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

113 citing papers in PubMed, 3 syntheses or guidelines pooled it.

  1. Pooled it
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  18. Extracellular vesicle-based therapeutic strategies for spinal cord injury.Extracellular vesicles and circulating nucleic acids · 2026
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  20. Article

53 more citing papers are in PubMed but not listed here.

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

5 authors.

Masahito NakazakiDepartment of Neurology, Yale University School of Medicine, New Haven, Connecticut, USA.ORCID 0000-0003-3155-5116
Tomonori MoritaDepartment of Neurology, Yale University School of Medicine, New Haven, Connecticut, USA.
Karen L LankfordDepartment of Neurology, Yale University School of Medicine, New Haven, Connecticut, USA.
Philip W AskenaseSection of Rheumatology, Allergy and Clinical Immunology, Department of Internal Medicine, Yale University School of Medicine, Connecticut, USA.
Jeffery D KocsisDepartment of Neurology, Yale University School of Medicine, New Haven, Connecticut, USA.

Funding

VA B7335RVA B9260L
6 · The paper itself

Abstract

Intravenous (IV) infusion of bone marrow-derived mesenchymal stem/stromal cells (MSCs) stabilizes the blood-spinal cord barrier (BSCB) and improves functional recovery in experimental models of spinal cord injury (SCI). Although IV delivered MSCs do not traffic to the injury site, IV delivered small extracellular vesicles (sEVs) derived from MSCs (MSC-sEVs) do and are taken up by a subset of M2 macrophages. To test whether sEVs released by MSCs are responsible for the therapeutic effects of MSCs, we tracked sEVs produced by IV delivered DiR-labelled MSCs (DiR-MSCs) after transplantation into SCI rats. We found that sEVs were released by MSCs in vivo, trafficked to the injury site, associated specifically with M2 macrophages and co-localized with exosome markers. Furthermore, while a single MSC injection was sufficient to improve locomotor recovery, fractionated dosing of MSC-sEVs over 3 days (F-sEVs) was required to achieve similar therapeutic effects. Infusion of F-sEVs mimicked the effects of single dose MSC infusion on multiple parameters including: increased expression of M2 macrophage markers, upregulation of transforming growth factor-beta (TGF-β), TGF-β receptors and tight junction proteins, and reduction in BSCB permeability. These data suggest that release of sEVs by MSCs over time induces a cascade of cellular responses leading to improved functional recovery.

Indexed as

AnimalsDisease Models, AnimalExtracellular VesiclesMacrophagesMaleMesenchymal Stem CellsRatsRats, Sprague-DawleySpinal Cord InjuriesTransforming Growth Factor betaUp-RegulationTransforming Growth Factor betablood-spinal cord barrierexosomesmacrophagesmesenchymal stem/stromal cellssmall extracellular vesiclesspinal cord injurytransforming growth factor-beta

Identifiers

PMID34478241
PMCPMC8408371

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.