Evidence map›Paper›PMID 24565698›Full record

Trial reportCirculation research2014

Autologous mesenchymal stem cells produce concordant improvements in regional function, tissue perfusion, and fibrotic burden when administered to patients undergoing coronary artery bypass grafting: The Prospective Randomized Study of Mesenchymal Stem Cell Therapy in Patients Undergoing Cardiac Surgery (PROMETHEUS) trial.

Vasileios Karantalis, Darcy L DiFede, Gary Gerstenblith, Si Pham, James Symes, Juan Pablo Zambrano, Joel Fishman, Pradip Pattany, Ian McNiece, John Conte and 17 more

Registry-linked trialOpen access · bronzeAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Circulation research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00587990 (A Phase I/II, Randomized, Double-Blinded, Placebo-Controlled Study of the Safety and Efficacy of Intramyocardial Injection of Autologous Human Mesenchymal Stem Cells), which is not on this map. Cited by 189 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
189citing papers in PubMed, 6 pooled it
37.8field-weighted citation impact, top 1% 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.

NCT00587990 phase1 / phase2terminatednot on this map

A Phase I/II, Randomized, Double-Blinded, Placebo-Controlled Study of the Safety and Efficacy of Intramyocardial Injection of Autologous Human Mesenchymal Stem Cells (MSCs) in Patients With Chronic Ischemic Left Ventricular Dysfunction Secondary to Myocardial Infarction (MI) Undergoing Cardiac Surgery for Coronary Artery Bypass Grafting (CABG)

TypeinterventionalSponsorJoshua M HareRan2007 to 2011Enrolled9ConditionsStem Cell Transplantation, Ventricular Dysfunction, LeftArmsLower dose mesenchymal stem cell (MSC) injection, Placebo, Higher dose MSC injection
3 · Its place in the literature

Who cites it

189 citing papers in PubMed, 6 syntheses or guidelines pooled it, 349 citations in OpenAlex.

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  18. Gene- and cell-based therapy in cardiovascular diseases.Journal of cardiovascular pharmacology · 2025
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129 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

27 authors at 2 institutions in 2 countries.

Vasileios KarantalisFrom the University of Miami Miller School of Medicine, Interdisciplinary Stem Cell Institute, Miami, FL (V.K., D.L.D., R.S., M.M., V.Y.S., A.W.L., J.M.H.); Johns Hopkins University, Cardiovascular Division, Baltimore, MD (G.G., S.S., E.B., J.D.-S., A.C.L.); University of Maryland, Cardiothoracic Surgery, Baltimore, MD (S.P., J.C.); Veterans Affairs Healthcare System, Cardiothoracic Surgery, Miami, FL (J.S., T.Z.K.); Jackson Health System, Cardiology, Miami, FL (J.P.Z.); University of Miami Miller School of Medicine, Radiology, Miami, FL (J.F., P.P.); University of Texas MD Anderson, Stem Cell Transplantation, Houston, TX (I.M.N.), Johns Hopkins University, Heart and Vascular Institute, Baltimore, MD (K.W.), Johns Hopkins University, Comprehensive Transplant Center (A.S.); University of Southern California, Internal Medicine, Los Angeles, CA (G.F.); Johns Hopkins University, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD (I.B.); EMMES Corporation, Rockville, MD (A.M.), University of Miami Miller School of Medicine, Hematology/Oncology, Miami, FL (J.B.); and University of Miami Miller School of Medicine, Cardiology, Miami, FL (T.Z.K., M.L.).
Darcy L DiFede
Gary Gerstenblith
Si Pham
James Symes
Juan Pablo Zambrano
Joel Fishman
Pradip Pattany
Ian McNiece
John Conte
Steven Schulman
Katherine Wu
Ashish Shah
Elayne Breton
Janice Davis-Sproul
Richard Schwarz
Gary Feigenbaum
Muzammil Mushtaq
Viky Y Suncion
Albert C Lardo
Ivan Borrello
Adam Mendizabal
Tomer Z Karas
John Byrnes
Maureen Lowery
Alan W Heldman
Joshua M Hare
Alkermes (Ireland) · IEUniversity of Miami · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
Institute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1M
Mesenchymal Stem Cell CardiomyoplastyU54HL081028 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI MARBAN, EDUARDO · 2005 to 2009
$12.1M
Cardioprotective Effect of Growth Hormone Releasing HormoneR01HL107110 · NHLBI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI HARE, JOSHUA M · 2011 to 2020
$5.9M
Cell Based Therapy for Non-Ischemic Dilated CardiomyopathyUM1HL113460 · NHLBI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI HARE, JOSHUA M · 2012 to 2018
$4.3M
Cellular Cardiomyoplasty for Chronic Heart FailureR01HL084275 · NHLBI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI HARE, JOSHUA M · 2007 to 2016
$3.8M
Stem Cells for Dilated CardiomyopathyR01HL110737 · NHLBI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI HARE, JOSHUA M · 2011 to 2015
$3.2M
Nitroso/redox balance in myocardial infarctionR01HL094849 · NHLBI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI HARE, JOSHUA M · 2009 to 2013
$2.2M
Autologous Adult Myocardial Cardioblasts to Treat Ischemic Heart FailureP20HL101443 · NHLBI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI HARE, JOSHUA M · 2010 to 2011
$1.5M
NCATS NIH HHS UL1 TR001079NCI NIH HHS P30 CA016672NHLBI NIH HHS HL081028NHLBI NIH HHS P20 HL101443NHLBI NIH HHS R01 HL084275NHLBI NIH HHS R01HL084275NHLBI NIH HHS R01 HL094849NHLBI NIH HHS R01 HL107110NHLBI NIH HHS R01 HL110737NHLBI NIH HHS R01 HL110737-01NHLBI NIH HHS U54 HL081028NHLBI NIH HHS UM1 HL113460
6 · The paper itself

Abstract

rationaleAlthough accumulating data support the efficacy of intramyocardial cell-based therapy to improve left ventricular (LV) function in patients with chronic ischemic cardiomyopathy undergoing CABG, the underlying mechanism and impact of cell injection site remain controversial. Mesenchymal stem cells (MSCs) improve LV structure and function through several effects including reducing fibrosis, neoangiogenesis, and neomyogenesis.

objectiveTo test the hypothesis that the impact on cardiac structure and function after intramyocardial injections of autologous MSCs results from a concordance of prorecovery phenotypic effects. METHODS AND

resultsSix patients were injected with autologous MSCs into akinetic/hypokinetic myocardial territories not receiving bypass graft for clinical reasons. MRI was used to measure scar, perfusion, wall thickness, and contractility at baseline, at 3, 6, and 18 months and to compare structural and functional recovery in regions that received MSC injections alone, revascularization alone, or neither. A composite score of MRI variables was used to assess concordance of antifibrotic effects, perfusion, and contraction at different regions. After 18 months, subjects receiving MSCs exhibited increased LV ejection fraction (+9.4 ± 1.7%, P=0.0002) and decreased scar mass (-47.5 ± 8.1%; P<0.0001) compared with baseline. MSC-injected segments had concordant reduction in scar size, perfusion, and contractile improvement (concordant score: 2.93 ± 0.07), whereas revascularized (0.5 ± 0.21) and nontreated segments (-0.07 ± 0.34) demonstrated nonconcordant changes (P<0.0001 versus injected segments).

conclusionsIntramyocardial injection of autologous MSCs into akinetic yet nonrevascularized segments produces comprehensive regional functional restitution, which in turn drives improvement in global LV function. These findings, although inconclusive because of lack of placebo group, have important therapeutic and mechanistic hypothesis-generating implications. CLINICAL TRIAL REGISTRATION URL: http://clinicaltrials.gov/show/NCT00587990. Unique identifier: NCT00587990.

Indexed as

Coronary Artery BypassCardiomyopathiesCell- and Tissue-Based TherapyCicatrixFibrosisFollow-Up StudiesHumansInjectionsMagnetic Resonance ImagingMaleMesenchymal Stem Cell TransplantationMiddle AgedMyocardial IschemiaMyocardiumPhenotypeProspective Studiescoronary artery bypassmesenchymal stromal cellsstem cell

Identifiers

PMID24565698
PMCPMC4104798
OpenAlexW2141844425

What OpenQuestion holds

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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.