Evidence map›Paper›PMID 26215972›Full record

ArticleJournal of the American Heart Association2015

Manganese-Enhanced Magnetic Resonance Imaging Enables In Vivo Confirmation of Peri-Infarct Restoration Following Stem Cell Therapy in a Porcine Ischemia-Reperfusion Model.

Rajesh Dash, Paul J Kim, Yuka Matsuura, Fumiaki Ikeno, Scott Metzler, Ngan F Huang, Jennifer K Lyons, Patricia K Nguyen, Xiaohu Ge, Cheryl Wong Po Foo and 5 more

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

Article in Journal of the American Heart Association, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.2field-weighted citation impact, top 14% 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

17 citing papers in PubMed, 24 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Manganese-Enhanced Magnetic Resonance Imaging of the Heart.Journal of magnetic resonance imaging : JMRI · 2023
    Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Manganese-enhanced TScientific reports · 2020
    Article
  10. Manganese-enhanced MRI of the myocardium.Heart (British Cardiac Society) · 2019
    Review
  11. Article
  12. Article
  13. A rapid TMagnetic resonance in medicine · 2018
    Article
  14. Review
  15. Article
  16. Article
  17. 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

15 authors at 4 institutions in 1 country.

Rajesh DashDivision of Cardiovascular Medicine, Stanford University, Stanford, CA (R.D., P.J.K., Y.M., F.I., S.M., N.F.H., J.K.L., P.K.N., X.G., M.V.M.C., J.C.W., A.C.Y., P.C.Y.) Stanford Cardiovascular Institute, Stanford University, Stanford, CA (R.D., N.F.H., P.K.N., M.V.M.C., J.C.W., P.C.Y.).
Paul J KimDivision of Cardiovascular Medicine, Stanford University, Stanford, CA (R.D., P.J.K., Y.M., F.I., S.M., N.F.H., J.K.L., P.K.N., X.G., M.V.M.C., J.C.W., A.C.Y., P.C.Y.).
Yuka MatsuuraDivision of Cardiovascular Medicine, Stanford University, Stanford, CA (R.D., P.J.K., Y.M., F.I., S.M., N.F.H., J.K.L., P.K.N., X.G., M.V.M.C., J.C.W., A.C.Y., P.C.Y.).
Fumiaki IkenoDivision of Cardiovascular Medicine, Stanford University, Stanford, CA (R.D., P.J.K., Y.M., F.I., S.M., N.F.H., J.K.L., P.K.N., X.G., M.V.M.C., J.C.W., A.C.Y., P.C.Y.).
Scott MetzlerDivision of Cardiovascular Medicine, Stanford University, Stanford, CA (R.D., P.J.K., Y.M., F.I., S.M., N.F.H., J.K.L., P.K.N., X.G., M.V.M.C., J.C.W., A.C.Y., P.C.Y.).
Ngan F HuangDivision of Cardiovascular Medicine, Stanford University, Stanford, CA (R.D., P.J.K., Y.M., F.I., S.M., N.F.H., J.K.L., P.K.N., X.G., M.V.M.C., J.C.W., A.C.Y., P.C.Y.) Stanford Cardiovascular Institute, Stanford University, Stanford, CA (R.D., N.F.H., P.K.N., M.V.M.C., J.C.W., P.C.Y.).
Jennifer K LyonsDivision of Cardiovascular Medicine, Stanford University, Stanford, CA (R.D., P.J.K., Y.M., F.I., S.M., N.F.H., J.K.L., P.K.N., X.G., M.V.M.C., J.C.W., A.C.Y., P.C.Y.).
Patricia K NguyenDivision of Cardiovascular Medicine, Stanford University, Stanford, CA (R.D., P.J.K., Y.M., F.I., S.M., N.F.H., J.K.L., P.K.N., X.G., M.V.M.C., J.C.W., A.C.Y., P.C.Y.) Stanford Cardiovascular Institute, Stanford University, Stanford, CA (R.D., N.F.H., P.K.N., M.V.M.C., J.C.W., P.C.Y.).
Xiaohu GeDivision of Cardiovascular Medicine, Stanford University, Stanford, CA (R.D., P.J.K., Y.M., F.I., S.M., N.F.H., J.K.L., P.K.N., X.G., M.V.M.C., J.C.W., A.C.Y., P.C.Y.).
Cheryl Wong Po FooBiocardia Inc, San Carlos, CA (C.W.P.F.).
Michael V McConnellDivision of Cardiovascular Medicine, Stanford University, Stanford, CA (R.D., P.J.K., Y.M., F.I., S.M., N.F.H., J.K.L., P.K.N., X.G., M.V.M.C., J.C.W., A.C.Y., P.C.Y.) Department of Electrical Engineering, Stanford University, Stanford, CA (M.V.M.C.) Stanford Cardiovascular Institute, Stanford University, Stanford, CA (R.D., N.F.H., P.K.N., M.V.M.C., J.C.W., P.C.Y.).
Joseph C WuDivision of Cardiovascular Medicine, Stanford University, Stanford, CA (R.D., P.J.K., Y.M., F.I., S.M., N.F.H., J.K.L., P.K.N., X.G., M.V.M.C., J.C.W., A.C.Y., P.C.Y.) Stanford Cardiovascular Institute, Stanford University, Stanford, CA (R.D., N.F.H., P.K.N., M.V.M.C., J.C.W., P.C.Y.).
Alan C YeungDivision of Cardiovascular Medicine, Stanford University, Stanford, CA (R.D., P.J.K., Y.M., F.I., S.M., N.F.H., J.K.L., P.K.N., X.G., M.V.M.C., J.C.W., A.C.Y., P.C.Y.).
Phillip HarnishEagle Vision Pharmaceutical Corp, Downingtown, PA (P.H.).
Phillip C YangDivision of Cardiovascular Medicine, Stanford University, Stanford, CA (R.D., P.J.K., Y.M., F.I., S.M., N.F.H., J.K.L., P.K.N., X.G., M.V.M.C., J.C.W., A.C.Y., P.C.Y.) Stanford Cardiovascular Institute, Stanford University, Stanford, CA (R.D., N.F.H., P.K.N., M.V.M.C., J.C.W., P.C.Y.).
Stanford Medicine · USStanford University · USCardiovascular Institute of the South · USBioCardia (United States) · US

Funding

Induced pluripotent stem cells in the understanding and treatment of heart diseaseU01HL099776 · NHLBI · STANFORD UNIVERSITY · PI LONGAKER, MICHAEL T, WU, JOSEPH C. · 2009 to 2015
$8.2M
Multi-Disciplinary Training Program in Cardiovascular Imaging at StanfordT32EB009035 · NIBIB · STANFORD UNIVERSITY · PI Koen Nieman, John M. Pauly · 2008 to 2026
$4.3M
Cell Characterization and Imaging for Regenerative Therapies in Ischemic DiseasesUM1HL113456 · NHLBI · STANFORD UNIVERSITY · PI YANG, PHILLIP CHUNG-MING · 2012 to 2018
$3.3M
Molecular Imaging of Targeted Cardiac Gene TherapyR01HL093172 · NHLBI · STANFORD UNIVERSITY · PI WU, JOSEPH C. · 2009 to 2015
$2.7M
Comprehensive in vivo MRI of mouse embryonic stem cell myocardial engraftment R01HL097516 · NHLBI · STANFORD UNIVERSITY · PI YANG, PHILLIP CHUNG-MING · 2009 to 2012
$1.6M
Molecular Imaging of Cardiac Stem Cell TherapyR01EB009689 · NIBIB · STANFORD UNIVERSITY · PI WU, JOSEPH C. · 2010 to 2013
$1.4M
Matrix-mediated endothelial differentiation of induced pluripotent stem cellsR00HL098688 · NHLBI · PALO ALTO VETERANS INSTIT FOR RESEARCH · PI HUANG, NGAN F. · 2013 to 2016
$742k
Cardiac Magnetic Resonance to Detect Apoptosis in Vivo using Magnetic Labeling.K08HL097022 · NHLBI · STANFORD UNIVERSITY · PI DASH, RAJESH · 2009 to 2013
$608k
NCRR NIH HHS 1S10RR 02902001NHLBI NIH HHS 1K08HL097022-01NHLBI NIH HHS 1R01HL097516-01NHLBI NIH HHS 5UM1 HL113456-02NHLBI NIH HHS R00HL098688NHLBI NIH HHS R01 HL093172NHLBI NIH HHS U01 HL099776NHLBI NIH HHS UM1 HL113456NIBIB NIH HHS R01 EB009689NIBIB NIH HHS T32 EB009035
6 · The paper itself

Abstract

backgroundThe exact mechanism of stem cell therapy in augmenting the function of ischemic cardiomyopathy is unclear. In this study, we hypothesized that increased viability of the peri-infarct region (PIR) produces restorative benefits after stem cell engraftment. A novel multimodality imaging approach simultaneously assessed myocardial viability (manganese-enhanced magnetic resonance imaging [MEMRI]), myocardial scar (delayed gadolinium enhancement MRI), and transplanted stem cell engraftment (positron emission tomography reporter gene) in the injured porcine hearts. METHODS AND

resultsTwelve adult swine underwent ischemia-reperfusion injury. Digital subtraction of MEMRI-negative myocardium (intrainfarct region) from delayed gadolinium enhancement MRI-positive myocardium (PIR and intrainfarct region) clearly delineated the PIR in which the MEMRI-positive signal reflected PIR viability. Human amniotic mesenchymal stem cells (hAMSCs) represent a unique population of immunomodulatory mesodermal stem cells that restored the murine PIR. Immediately following hAMSC delivery, MEMRI demonstrated an increased PIR viability signal compared with control. Direct PIR viability remained higher in hAMSC-treated hearts for >6 weeks. Increased PIR viability correlated with improved regional contractility, left ventricular ejection fraction, infarct size, and hAMSC engraftment, as confirmed by immunocytochemistry. Increased MEMRI and positron emission tomography reporter gene signal in the intrainfarct region and the PIR correlated with sustained functional augmentation (global and regional) within the hAMSC group (mean change, left ventricular ejection fraction: hAMSC 85±60%, control 8±10%; P<0.05) and reduced chamber dilatation (left ventricular end-diastole volume increase: hAMSC 24±8%, control 110±30%; P<0.05).

conclusionsThe positron emission tomography reporter gene signal of hAMSC engraftment correlates with the improved MEMRI signal in the PIR. The increased MEMRI signal represents PIR viability and the restorative potential of the injured heart. This in vivo multimodality imaging platform represents a novel, real-time method of tracking PIR viability and stem cell engraftment while providing a mechanistic explanation of the therapeutic efficacy of cardiovascular stem cells.

Indexed as

Mesenchymal Stem Cell TransplantationAnimalsCell SurvivalDisease Models, AnimalGadoliniumHumansImmunohistochemistryMagnetic Resonance ImagingManganeseMiceMyocardiumPositron-Emission TomographyReperfusion InjuryStem CellsSwineTissue SurvivalGadoliniumManganeseischemia–reperfusion injurymagnetic resonance imagingmanganese‐enhanced magnetic resonance imagingperi‐infarct region imagingstem cell imaging

Identifiers

PMID26215972
PMCPMC4608088
OpenAlexW1917508179

What OpenQuestion holds

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Registered trials

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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.