Evidence map›Paper›PMID 38096818›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2024

Extracellular vesicles from differentiated stem cells contain novel proangiogenic miRNAs and induce angiogenic responses at low doses.

Despoina Kesidou, Matthew Bennett, João P Monteiro, Ian R McCracken, Eftychia Klimi, Julie Rodor, Alison Condie, Scott Cowan, Andrea Caporali, Jan B M Wit and 4 more

Open access · hybridAbstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.3field-weighted citation impact, top 11% 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

14 citing papers in PubMed, 15 citations in OpenAlex.

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  10. Extracellular vesicles from cartilage progenitors stimulate type II collagen expression and wound healing in meniscal cells.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2025
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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

14 authors at 6 institutions in 3 countries.

Despoina KesidouCentre for Cardiovascular Science, University of Edinburgh, Edinburgh EH16 4TJ, UK.
Matthew BennettCentre for Cardiovascular Science, University of Edinburgh, Edinburgh EH16 4TJ, UK.
João P MonteiroCentre for Cardiovascular Science, University of Edinburgh, Edinburgh EH16 4TJ, UK; Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Ian R McCrackenCentre for Cardiovascular Science, University of Edinburgh, Edinburgh EH16 4TJ, UK; Institute of Developmental and Regenerative Medicine, Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford OX3 7TY, UK.
Eftychia KlimiCentre for Cardiovascular Science, University of Edinburgh, Edinburgh EH16 4TJ, UK.
Julie RodorCentre for Cardiovascular Science, University of Edinburgh, Edinburgh EH16 4TJ, UK.
Alison CondieScottish National Blood Transfusion Service, Edinburgh EH14 4BE, UK.
Scott CowanScottish National Blood Transfusion Service, Edinburgh EH14 4BE, UK.
Andrea CaporaliCentre for Cardiovascular Science, University of Edinburgh, Edinburgh EH16 4TJ, UK.
Jan B M WitMirabilis Therapeutics BV, Maastricht, the Netherlands.
Joanne C MountfordScottish National Blood Transfusion Service, Edinburgh EH14 4BE, UK.
Mairi BrittanCentre for Cardiovascular Science, University of Edinburgh, Edinburgh EH16 4TJ, UK.
Abdelaziz BeqqaliCentre for Cardiovascular Science, University of Edinburgh, Edinburgh EH16 4TJ, UK. Electronic address: a.beqqali@ed.ac.uk.
Andrew H BakerCentre for Cardiovascular Science, University of Edinburgh, Edinburgh EH16 4TJ, UK; CARIM Institute, University of Maastricht, Maastricht 6229HX, the Netherlands. Electronic address: andy.baker@ed.ac.uk.
University of Edinburgh · GBScottish National Blood Transfusion Service · GBCristal Therapeutics (Netherlands) · NLMaastricht University · NLStanford University · USUniversity of Oxford · GB

Funding

British Heart Foundation CH/11/2/28733British Heart Foundation FS/16/4/31831British Heart Foundation PG/22/10916British Heart Foundation RG/20/5/34796Wellcome Trust
6 · The paper itself

Abstract

Extracellular vesicles (EVs) released from healthy endothelial cells (ECs) have shown potential for promoting angiogenesis, but their therapeutic efficacy remains poorly understood. We have previously shown that transplantation of a human embryonic stem cell-derived endothelial cell product (hESC-ECP), promotes new vessel formation in acute ischemic disease in mice, likely via paracrine mechanism(s). Here, we demonstrated that EVs from hESC-ECPs (hESC-eEVs) significantly increased EC tube formation and wound closure in vitro at ultralow doses, whereas higher doses were ineffective. More important, EVs isolated from the mesodermal stage of the differentiation (hESC-mEVs) had no effect. Small RNA sequencing revealed that hESC-eEVs have a unique transcriptomic profile and are enriched in known proangiogenic microRNAs (miRNAs, miRs). Moreover, an in silico analysis identified three novel hESC-eEV-miRNAs with potential proangiogenic function. Differential expression analysis suggested that two of those, miR-4496 and miR-4691-5p, are highly enriched in hESC-eEVs. Overexpression of miR-4496 or miR-4691-5p resulted in increased EC tube formation and wound closure in vitro, validating the novel proangiogenic function of these miRNAs. In summary, we demonstrated that hESC-eEVs are potent inducers of EC angiogenic response at ultralow doses and contain a unique EV-associated miRNA repertoire, including miR-4496 and miR-4691-5p, with novel proangiogenic function.

Indexed as

Extracellular VesiclesMicroRNAsAnimalsCell DifferentiationEndothelial CellsHumansMiceStem CellsMicroRNAsangiogenesisdeliverydose responseendothelial cell differentiationextracellular vesiclesmicroRNAmiR-4496miR-4691-5pmyocardial infarctionvasculature

Identifiers

PMID38096818
PMCPMC10787168
OpenAlexW4389687839

What OpenQuestion holds

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LicenceCC BY
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.