Evidence map›Paper›PMID 18849336›Full record

ArticleAmerican journal of physiology. Heart and circulatory physiology2008

VEGF is critical for stem cell-mediated cardioprotection and a crucial paracrine factor for defining the age threshold in adult and neonatal stem cell function.

Troy A Markel, Yue Wang, Jeremy L Herrmann, Paul R Crisostomo, Meijing Wang, Nathan M Novotny, Christine M Herring, Jiangning Tan, Tim Lahm, Daniel R Meldrum

Registry-linked trialOpen access · greenAbstract readComparative Study
In one paragraph

Article in American journal of physiology. Heart and circulatory physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02863926 (Safety and Efficacy of Concentrated Autologous Concentrated Bone Marrow Aspirate), which is not on this map. Cited by 73 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed, 1 pooled it
6.0field-weighted citation impact, top 3% 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.

NCT02863926 phase1completednot on this mapstarted 2017, after this paper: background citation

Safety and Efficacy of Concentrated Autologous Concentrated Bone Marrow Aspirate (cBMA) in Preventing Wound Complications in Below Knee Amputation (BKA) (The MarrowCHAMP Study)

TypeinterventionalSponsorMichael MurphyRan2017 to 2018Enrolled6ConditionsPeripheral Artery Disease, Vascular Disease, Critical Limb IschemiaArmsInjection of cBMA aspirate into the index leg
3 · Its place in the literature

Who cites it

73 citing papers in PubMed, 1 synthesis or guideline pooled it, 148 citations in OpenAlex.

  1. Pooled it
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  5. Article
  6. Review
  7. Article
  8. Article
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  11. Article
  12. Functions of Mesenchymal Stem Cells in Cardiac Repair.Advances in experimental medicine and biology · 2021
    Article
  13. Review
  14. Article
  15. Locoregional delivery of stem cell-based therapies.Science translational medicine · 2020
    Review
  16. Article
  17. Review
  18. Article
  19. Article
  20. Review

13 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

10 authors at 2 institutions in 1 country.

Troy A MarkelDepartment of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Yue Wang
Jeremy L Herrmann
Paul R Crisostomo
Meijing Wang
Nathan M Novotny
Christine M Herring
Jiangning Tan
Tim Lahm
Daniel R Meldrum
Indiana University School of MedicinePulmonary and Critical Care Associates · US

Funding

TNRF1 Signaling Resistance in Ischemic Human Female MyocardiumR01HL085595 · NHLBI · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI MELDRUM, DANIEL R · 2007 to 2010
$1.8M
Progenitor cell pretreatment against acute surgical I/RR01GM070628 · NIGMS · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI MELDRUM, DANIEL R · 2004 to 2008
$1.5M
TNFR1 and Sex Hormone Signaling in Myocardial IschemiaF32HL085982 · NHLBI · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI MARKEL, TROY A · 2006 to 2007
$95k
NHLBI NIH HHS F32-HL-085982NHLBI NIH HHS K99/R00-HL-0876077-01NHLBI NIH HHS R01-HL-085595NIGMS NIH HHS R01-GM-070628
6 · The paper itself

Abstract

Bone marrow mesenchymal stem cells (MSCs) may be a novel treatment modality for organ ischemia, possibly through the release of beneficial paracrine factors. However, an age threshold likely exists as to when MSCs gain their beneficial protective properties. We hypothesized that 1) VEGF would be a crucial stem cell paracrine mediator in providing postischemic myocardial protection and 2) small-interfering (si)RNA ablation of VEGF in adult MSCs (aMSCs) would equalize the differences observed between aMSC- and neonatal stem cell (nMSC)-mediated cardioprotection. Female adult Sprague-Dawley rat hearts were subjected to ischemia-reperfusion injury via Langendorff-isolated heart preparation (15 min equilibration, 25 min ischemia, and 60 min reperfusion). MSCs were harvested from adult and 2.5-wk-old neonatal mice and cultured under normal conditions. VEGF was knocked down in both cell lines by VEGF siRNA. Immediately before ischemia, one million aMSCs or nMSCs with or without VEGF knockdown were infused into the coronary circulation. The cardiac functional parameters were recorded. VEGF in cell supernatants was measured via ELISA. aMSCs produced significantly more VEGF than nMSCs and were noted to increase postischemic myocardial recovery compared with nMSCs. The knockdown of VEGF significantly decreased VEGF production in both cell lines, and the pretreatment of these cells impaired stem cell-mediated myocardial function. The knockdown of VEGF in adult stem cells equalized the myocardial functional differences observed between adult and neonatal stem cells. Therefore, VEGF is a critical paracrine mediator in facilitating postischemic myocardial recovery and likely plays a role in mediating the observed age threshold during stem cell therapy.

Indexed as

Mesenchymal Stem Cell TransplantationParacrine CommunicationAdult Stem CellsAge FactorsAgingAnimalsAnimals, NewbornCells, CulturedDisease Models, AnimalFemaleMesenchymal Stem CellsMiceMice, Inbred C57BLMyocardial ContractionMyocardial Reperfusion InjuryRatsRNA, Small InterferingVascular Endothelial Growth Factor Avascular endothelial growth factor A, mouse

Identifiers

PMID18849336
PMCPMC2614539
OpenAlexW2149376334

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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.