Evidence map›Paper›PMID 24736402›Full record

ArticleStem cells translational medicine2014

Cobalt protoporphyrin pretreatment protects human embryonic stem cell-derived cardiomyocytes from hypoxia/reoxygenation injury in vitro and increases graft size and vascularization in vivo.

Jun Luo, Matthew S Weaver, Baohong Cao, James E Dennis, Benjamin Van Biber, Michael A Laflamme, Margaret D Allen

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stem cells translational medicine, 2014. 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
2.5field-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, 25 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Review
  10. Review
  11. Review
  12. Article
  13. Article
  14. 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

7 authors at 2 institutions in 1 country.

Jun LuoMatrix Biology Program, Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA; Departments of Pathology and Surgery, University of Washington School of Medicine, Seattle, Washington, USA.
Matthew S WeaverMatrix Biology Program, Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA; Departments of Pathology and Surgery, University of Washington School of Medicine, Seattle, Washington, USA.
Baohong CaoMatrix Biology Program, Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA; Departments of Pathology and Surgery, University of Washington School of Medicine, Seattle, Washington, USA.
James E DennisMatrix Biology Program, Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA; Departments of Pathology and Surgery, University of Washington School of Medicine, Seattle, Washington, USA.
Benjamin Van BiberMatrix Biology Program, Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA; Departments of Pathology and Surgery, University of Washington School of Medicine, Seattle, Washington, USA.
Michael A LaflammeMatrix Biology Program, Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA; Departments of Pathology and Surgery, University of Washington School of Medicine, Seattle, Washington, USA.
Margaret D AllenMatrix Biology Program, Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA; Departments of Pathology and Surgery, University of Washington School of Medicine, Seattle, Washington, USA mallen@benaroyaresearch.org.
Virginia Mason Medical Center · USUniversity of Washington · US

Funding

Engineered Cardiac Morphogenesis-Stem Cells and ScaffoldsR01HL064387 · NHLBI · UNIVERSITY OF WASHINGTON · PI RATNER, BUDDY D · 2006 to 2010
$10.2M
Humna ES Cells for Cardiac Tissue EngineeringR24HL064387 · NHLBI · UNIVERSITY OF WASHINGTON · PI RATNER, BUDDY D · 2000 to 2004
$9.4M
Engineered Atrium: New Autologous Cells for Heart RepairR01HL086709 · NHLBI · BENAROYA RESEARCH INST AT VIRGINIA MASON · PI ALLEN, MARGARET D · 2008 to 2011
$2.5M
NHLBI NIH HHS HL086709NHLBI NIH HHS HL64387NHLBI NIH HHS R01 HL064387NHLBI NIH HHS R01 HL086709NHLBI NIH HHS R24 HL064387
6 · The paper itself

Abstract

Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) can regenerate infarcted myocardium. However, when implanted into acutely infarcted hearts, few cells survive the first week postimplant. To improve early graft survival, hESC-CMs were pretreated with cobalt protoporphyrin (CoPP), a transcriptional activator of cytoprotective heme oxygenase-1 (HO-1). When hESC-CMs were challenged with an in vitro hypoxia/reoxygenation injury, mimicking cell transplantation into an ischemic site, survival was significantly greater among cells pretreated with CoPP versus phosphate-buffered saline (PBS)-pretreated controls. Compared with PBS-pretreated cells, CoPP-pretreated hESC-CM preparations exhibited higher levels of HO-1 expression, Akt phosphorylation, and vascular endothelial growth factor production, with reduced apoptosis, and a 30% decrease in intracellular reactive oxygen species. For in vivo translation, 1 × 10(7) hESC-CMs were pretreated ex vivo with CoPP or PBS and then injected intramyocardially into rat hearts immediately following acute infarction (permanent coronary ligation). At 1 week, hESC-CM content, assessed by quantitative polymerase chain reaction for human Alu sequences, was 17-fold higher in hearts receiving CoPP- than PBS-pretreated cells. On histomorphometry, cardiomyocyte graft size was 2.6-fold larger in hearts receiving CoPP- than PBS-pretreated cells, occupying up to 12% of the ventricular area. Vascular density of host-perfused human-derived capillaries was significantly greater in grafts composed of CoPP- than PBS-pretreated cells. Taken together, these experiments demonstrate that ex vivo pretreatment of hESC-CMs with a single dose of CoPP before intramyocardial implantation more than doubled resulting graft size and improved early graft vascularization in acutely infarcted hearts. These findings open the door for delivery of these, or other, stem cells during acute interventional therapy following myocardial infarction or ischemia.

Indexed as

RegenerationAnimalsApoptosisCell DifferentiationCell LineCell ProliferationDisease Models, AnimalEmbryonic Stem CellsEnzyme InductionFemaleGraft SurvivalHeme Oxygenase-1HumansMaleMyocardial InfarctionMyocardial Reperfusion InjurycobaltiprotoporphyrinHeme Oxygenase-1HMOX1 protein, humanProto-Oncogene Proteins c-aktProtoporphyrinsReactive Oxygen SpeciesVascular Endothelial Growth Factor AVEGFA protein, humanAcute myocardial infarctionCell therapyHeme oxygenase-1Human embryonic stem cellInfarct repairPreconditioning

Identifiers

PMID24736402
PMCPMC4039456
OpenAlexW2151184946

What OpenQuestion holds

Textmetadata
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.