Evidence map›Paper›PMID 27806113›Full record

ArticlePloS one2016

Inhibiting Extracellular Vesicle Release from Human Cardiosphere Derived Cells with Lentiviral Knockdown of nSMase2 Differentially Effects Proliferation and Apoptosis in Cardiomyocytes, Fibroblasts and Endothelial Cells In Vitro.

Jennifer K Lang, Rebeccah F Young, Hashmat Ashraf, John M Canty

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
4.2field-weighted citation impact, top 6% 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

36 citing papers in PubMed, 57 citations in OpenAlex.

  1. Article
  2. Review
  3. Neutral sphingomyelinase 2: A promising drug target for CNS disease.Advances in pharmacology (San Diego, Calif.) · 2025
    Review
  4. Surface engineering enhances the therapeutic potential of systemically delivered extracellular vesicles following acute myocardial infarction.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024
    Article
  5. Review
  6. Review
  7. Review
  8. Review
  9. Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. Review
  15. Review
  16. Mesenchymal stem cell-derived extracellular vesicles in the failing heart: past, present, and future.American journal of physiology. Heart and circulatory physiology · 2021
    Review
  17. Review
  18. Review
  19. Article
  20. Article
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

4 authors at 3 institutions in 1 country.

Jennifer K LangDepartment of Medicine, Division of Cardiology, Jacobs School of Medicine and Biomedical Sciences, Buffalo, N.Y, 14203, United States of America.ORCID http://orcid.org/0000-0002-6221-8625
Rebeccah F YoungDepartment of Medicine, Division of Cardiology, Jacobs School of Medicine and Biomedical Sciences, Buffalo, N.Y, 14203, United States of America.
Hashmat AshrafDepartment of Cardiothoracic Surgery, Kaleida Health, Buffalo, N.Y, 14203, United States of America.
John M CantyDepartment of Medicine, Division of Cardiology, Jacobs School of Medicine and Biomedical Sciences, Buffalo, N.Y, 14203, United States of America.
Jacobs Institute · USKaleida Health · USVA Western New York Healthcare System · US

Funding

University of Buffalo Clinical and Translational Science Institute - Supplement SchulyerUL1TR001412 · NCATS · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI MURPHY, TIMOTHY F · 2015 to 2024
$33.8M
Metabolic Adaptation and Functional Recovery of Hibernating MyocardiumR01HL061610 · NHLBI · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI CANTY, JOHN M · 2000 to 2018
$6.0M
CHRONIC ADAPTATIONS TO MYOCARDIAL ISCHEMIAR01HL055324 · NHLBI · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI CANTY, JOHN M · 1996 to 2014
$4.2M
NCATS NIH HHS UL1 TR001412NHLBI NIH HHS R01 HL055324NHLBI NIH HHS R01 HL061610
6 · The paper itself

Abstract

Numerous studies have shown a beneficial effect of cardiosphere-derived cell (CDC) therapy on regeneration of injured myocardium. Paracrine signaling by CDC secreted exosomes may contribute to improved cardiac function. However, it has not yet been demonstrated by a genetic approach that exosome release contributes to the therapeutic effect of transplanted CDCs. By employing a lentiviral knockdown (KD) strategy against neutral spingomyelinase 2 (nSMase2), a crucial gene in exosome secretion, we have defined the role of physiologically secreted human CDC-derived exosomes on cardiac fibroblast, endothelial cell and primary cardiomyocyte proliferation, cell death, migration and angiogenesis using a series of in vitro coculture assays. We found that secretion of hCDC-derived exosomes was effectively inhibited by nSMase2 lentiviral KD and shRNAi expression was stable and constitutive. hCDC exosome release contributed to the angiogenic and pro-migratory effects of hCDCs on HUVECs, decreased proliferation of fibroblasts, and decreased apoptosis of cardiomyocytes. These in vitro reactions support a role for exosome secretion as a paracrine mechanism of stem cell-mediated cardiac repair in vivo. Importantly, we have established a novel tool to test constitutive inhibition of exosome secretion in stem cell populations in animal models of cardiac disease.

Indexed as

ApoptosisCell ProliferationCells, CulturedCoculture TechniquesEndothelial CellsExtracellular VesiclesFibroblastsGene Knockdown TechniquesHumansIn Vitro TechniquesLentivirusMyocytes, CardiacParacrine CommunicationSphingomyelin PhosphodiesteraseSMPD3 protein, humanSphingomyelin Phosphodiesterase

Identifiers

PMID27806113
PMCPMC5091915
OpenAlexW2548723006

What OpenQuestion holds

Textmetadata
LicenceCC0
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.