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Original Research

A Detailed Analysis of Bone Marrow from Patients with Ischemic Heart Disease and Left Ventricular Dysfunction: BM CD34, CD11b and Clonogenic Capacity as Biomarkers for Clinical Outcomes

Christopher R Cogle, Elizabeth Wise, Amy M Meacham, Claudia Zierold, Jay H Traverse, Timothy D Henry, Emerson C Perin, James T Willerson, Stephen G Ellis, Marjorie A Carlson, David Zhao, Roberto Bolli, John P Cooke, Saif Anwaruddin, Aruni Bhatnagar, Maria Cabreira-Graca, Maria B Grant, Dejian Lai, Lemuel Moyé, Ray F Ebert, Rachel E Olson, Shelly L Sayre, Ivonne H Schulman, Edward W Scott, Robert D Simari, Carl J Pepine, Doris Taylor
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https://doi.org/10.1161/CIRCRESAHA.115.304353
Circulation Research. 2014;CIRCRESAHA.114.304353
Originally published August 18, 2014
Christopher R Cogle
Medicine, Hematology and Oncology, University of Florida College of Medicine
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Elizabeth Wise
University of Florida College of Medicine
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Amy M Meacham
University of Florida College of Medicine
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Claudia Zierold
University of Minnesota School of Medicine
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Jay H Traverse
Cardiology, Minneapolis Heart Institute
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Timothy D Henry
Cardiology, Minneapolis Heart Institute
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Emerson C Perin
Texas Heart Institute
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James T Willerson
Texas Heart Institute
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Stephen G Ellis
Cardiology, Cleveland Clinic Foundation
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Marjorie A Carlson
Biomedical Engineering, University of Minnesota School of Medicine
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David Zhao
Vanderbilt University School of Medicine
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Roberto Bolli
University of Louisville
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John P Cooke
Cardiovascular Sciences, Houston Methodist Research Institute
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Saif Anwaruddin
University of Pennsylvania School of Medicine
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Aruni Bhatnagar
Cardiovascular Medicine, University of Louisville
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Maria Cabreira-Graca
Texas Heart Insititute
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Maria B Grant
Pharmacology Therapeutics, University of Florida College of Medicine
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Dejian Lai
University of Texas School of Public Health
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Lemuel Moyé
Biostatistics, University of Texas School of Public Health
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  • For correspondence: lemmoye@msn.com
Ray F Ebert
National Heart, Lung and Blood Institute
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Rachel E Olson
Minneapolis Heart Institute Foundation at Abbott
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Shelly L Sayre
Coordinating Center for Clinical Trials, University of Texas School of Public Health
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Ivonne H Schulman
Nephrology-Hypertension, University of Miami School of Medicine
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Edward W Scott
Molecular Genetics and Microbiology, University of Florida College of Medicine
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Robert D Simari
Mayo Clinic College of Medicine
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Carl J Pepine
Medicine, University of Florida College of Medicine
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Doris Taylor
Regenerative Medicine Research, Texas Heart Institute
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Abstract

Rationale: Bone marrow (BM) cell therapy for ischemic heart disease (IHD) has shown mixed results. Before the full potency of BM cell therapy can be realized, it is essential to understand the BM niche following acute myocardial infarction (AMI).

Objective: To study the BM composition in patients with IHD and severe left ventricular dysfunction (LVD).

Methods and Results: BM from 280 patients with IHD and LVD were analyzed for cell subsets by flow cytometry and colony assays. BM CD34+ cell percentage was decreased 7 days after AMI (mean of 1.9% vs. 2.3-2.7% in other cohorts; p < 0.05). BM-derived endothelial colonies were significantly decreased (p < 0.05). Increased BM CD11b+ cells associated with worse left ventricular ejection fraction (LVEF) after AMI (p < 0.05). While increased BM CD34+ percentage associated with greater improvement in LVEF (+9.9% vs. +2.3%, p=0.03, for AMI patients; and +6.6% vs. -0.02%, p=0.021 for chronic IHD patients), decreased BM CD34+ percentage in chronic IHD patients correlated with decrement in LVEF after cell therapy (-2.9% vs. +0.7%, p=0.0355).

Conclusions: In this study we show a heterogeneous mixture of BM cell subsets, decreased endothelial colony capacity, a CD34+ cell nadir seven days after AMI, a negative correlation between CD11b percentage and post-infarct LVEF, and positive correlation of CD34 percentage with change in LVEF after cell therapy. These results serve as a possible basis for the small clinical improvement seen in autologous BM cell therapy trials and support selection of potent cell subsets and/or reversal of co-morbid BM impairment.

  • myocardial infarction
  • blood cell
  • angiogenesis
  • bone marrow
  • stem cell
  • Received May 19, 2014.
  • Revision received August 15, 2014.
  • Accepted August 18, 2014.
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    A Detailed Analysis of Bone Marrow from Patients with Ischemic Heart Disease and Left Ventricular Dysfunction: BM CD34, CD11b and Clonogenic Capacity as Biomarkers for Clinical Outcomes
    Christopher R Cogle, Elizabeth Wise, Amy M Meacham, Claudia Zierold, Jay H Traverse, Timothy D Henry, Emerson C Perin, James T Willerson, Stephen G Ellis, Marjorie A Carlson, David Zhao, Roberto Bolli, John P Cooke, Saif Anwaruddin, Aruni Bhatnagar, Maria Cabreira-Graca, Maria B Grant, Dejian Lai, Lemuel Moyé, Ray F Ebert, Rachel E Olson, Shelly L Sayre, Ivonne H Schulman, Edward W Scott, Robert D Simari, Carl J Pepine and Doris Taylor
    Circulation Research. 2014;CIRCRESAHA.114.304353, originally published August 18, 2014
    https://doi.org/10.1161/CIRCRESAHA.115.304353

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    A Detailed Analysis of Bone Marrow from Patients with Ischemic Heart Disease and Left Ventricular Dysfunction: BM CD34, CD11b and Clonogenic Capacity as Biomarkers for Clinical Outcomes
    Christopher R Cogle, Elizabeth Wise, Amy M Meacham, Claudia Zierold, Jay H Traverse, Timothy D Henry, Emerson C Perin, James T Willerson, Stephen G Ellis, Marjorie A Carlson, David Zhao, Roberto Bolli, John P Cooke, Saif Anwaruddin, Aruni Bhatnagar, Maria Cabreira-Graca, Maria B Grant, Dejian Lai, Lemuel Moyé, Ray F Ebert, Rachel E Olson, Shelly L Sayre, Ivonne H Schulman, Edward W Scott, Robert D Simari, Carl J Pepine and Doris Taylor
    Circulation Research. 2014;CIRCRESAHA.114.304353, originally published August 18, 2014
    https://doi.org/10.1161/CIRCRESAHA.115.304353
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