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 Carlson, David X M Zhao, Roberto Bolli, John P. Cooke, Saif Anwaruddin, Aruni Bhatnagar, Maria Cabreira-Graca, Maria B. Grant, Dejian Lai, Lemuel A. Moyé, Ray F. Ebert & 7 others Rachel E. Olson, Shelly L. Sayre, Ivonne H. Schulman, Edward W. Scott, Robert D. Simari, Carl J. Pepine, Doris A. Taylor

Research output: Contribution to journalArticle

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 & 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. CLINICAL TRIAL REGISTRATIONS: clinicaltrials.gov Identifiers: NCT00684021, NCT00684060, NCT00824005.

Original languageEnglish (US)
JournalCirculation Research
DOIs
StateAccepted/In press - Aug 20 2014

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Left Ventricular Dysfunction
Myocardial Ischemia
Bone Marrow Cells
Biomarkers
Bone Marrow
Cell- and Tissue-Based Therapy
Stroke Volume
Myocardial Infarction
Flow Cytometry
Clinical Trials

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology

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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. / Cogle, Christopher R.; Wise, Elizabeth; Meacham, Amy M.; Zierold, Claudia; Traverse, Jay H.; Henry, Timothy D.; Perin, Emerson C.; Willerson, James T.; Ellis, Stephen G.; Carlson, Marjorie; Zhao, David X M; Bolli, Roberto; Cooke, John P.; Anwaruddin, Saif; Bhatnagar, Aruni; Cabreira-Graca, Maria; Grant, Maria B.; Lai, Dejian; Moyé, Lemuel A.; Ebert, Ray F.; Olson, Rachel E.; Sayre, Shelly L.; Schulman, Ivonne H.; Scott, Edward W.; Simari, Robert D.; Pepine, Carl J.; Taylor, Doris A.

In: Circulation Research, 20.08.2014.

Research output: Contribution to journalArticle

Cogle, CR, Wise, E, Meacham, AM, Zierold, C, Traverse, JH, Henry, TD, Perin, EC, Willerson, JT, Ellis, SG, Carlson, M, Zhao, DXM, Bolli, R, Cooke, JP, Anwaruddin, S, Bhatnagar, A, Cabreira-Graca, M, Grant, MB, Lai, D, Moyé, LA, Ebert, RF, Olson, RE, Sayre, SL, Schulman, IH, Scott, EW, Simari, RD, Pepine, CJ & Taylor, DA 2014, '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', Circulation Research. https://doi.org/10.1161/CIRCRESAHA.115.304353
Cogle, Christopher R. ; Wise, Elizabeth ; Meacham, Amy M. ; Zierold, Claudia ; Traverse, Jay H. ; Henry, Timothy D. ; Perin, Emerson C. ; Willerson, James T. ; Ellis, Stephen G. ; Carlson, Marjorie ; Zhao, David X M ; Bolli, Roberto ; Cooke, John P. ; Anwaruddin, Saif ; Bhatnagar, Aruni ; Cabreira-Graca, Maria ; Grant, Maria B. ; Lai, Dejian ; Moyé, Lemuel A. ; Ebert, Ray F. ; Olson, Rachel E. ; Sayre, Shelly L. ; Schulman, Ivonne H. ; Scott, Edward W. ; Simari, Robert D. ; Pepine, Carl J. ; Taylor, Doris A. / 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. In: Circulation Research. 2014.
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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 & 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. CLINICAL TRIAL REGISTRATIONS: clinicaltrials.gov Identifiers: NCT00684021, NCT00684060, NCT00824005.",
author = "Cogle, {Christopher R.} and Elizabeth Wise and Meacham, {Amy M.} and Claudia Zierold and Traverse, {Jay H.} and Henry, {Timothy D.} and Perin, {Emerson C.} and Willerson, {James T.} and Ellis, {Stephen G.} and Marjorie Carlson and Zhao, {David X M} and Roberto Bolli and Cooke, {John P.} and Saif Anwaruddin and Aruni Bhatnagar and Maria Cabreira-Graca and Grant, {Maria B.} and Dejian Lai and Moy{\'e}, {Lemuel A.} and Ebert, {Ray F.} and Olson, {Rachel E.} and Sayre, {Shelly L.} and Schulman, {Ivonne H.} and Scott, {Edward W.} and Simari, {Robert D.} and Pepine, {Carl J.} and Taylor, {Doris A.}",
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T1 - A detailed analysis of bone marrow from patients with ischemic heart disease and left ventricular dysfunction

T2 - BM CD34, CD11B and clonogenic capacity as biomarkers for clinical outcomes

AU - Cogle, Christopher R.

AU - Wise, Elizabeth

AU - Meacham, Amy M.

AU - Zierold, Claudia

AU - Traverse, Jay H.

AU - Henry, Timothy D.

AU - Perin, Emerson C.

AU - Willerson, James T.

AU - Ellis, Stephen G.

AU - Carlson, Marjorie

AU - Zhao, David X M

AU - Bolli, Roberto

AU - Cooke, John P.

AU - Anwaruddin, Saif

AU - Bhatnagar, Aruni

AU - Cabreira-Graca, Maria

AU - Grant, Maria B.

AU - Lai, Dejian

AU - Moyé, Lemuel A.

AU - Ebert, Ray F.

AU - Olson, Rachel E.

AU - Sayre, Shelly L.

AU - Schulman, Ivonne H.

AU - Scott, Edward W.

AU - Simari, Robert D.

AU - Pepine, Carl J.

AU - Taylor, Doris A.

PY - 2014/8/20

Y1 - 2014/8/20

N2 - 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 & 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. CLINICAL TRIAL REGISTRATIONS: clinicaltrials.gov Identifiers: NCT00684021, NCT00684060, NCT00824005.

AB - 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 & 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. CLINICAL TRIAL REGISTRATIONS: clinicaltrials.gov Identifiers: NCT00684021, NCT00684060, NCT00824005.

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U2 - 10.1161/CIRCRESAHA.115.304353

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