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 Da Graca Cabreira-Hansen, Maria B. Grant, Dejian Lai, Lem Moyé, Ray F. EbertRachel E. Olson, Shelly L. Sayre, Ivonne H. Schulman, Raphael C. Bosse, Edward W. Scott, Robert D. Simari, Carl J. Pepine, Doris A. Taylor

Research output: Contribution to journalArticle

47 Scopus citations

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 after acute myocardial infarction (AMI). Objective: To study the BM composition in patients with IHD and severe left ventricular (LV) dysfunction. Methods and Results: BM from 280 patients with IHD and LV dysfunction 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% versus 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 LV ejection fraction (LVEF) after AMI (P<0.05). Increased BM CD34+ percentage associated with greater improvement in LVEF (+9.9% versus +2.3%; P=0.03, for patients with AMI and +6.6% versus-0.02%; P=0.021 for patients with chronic IHD). In addition, decreased BM CD34+ percentage in patients with chronic IHD correlated with decrement in LVEF (-2.9% versus +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 7 days after AMI, a negative correlation between CD11b percentage and postinfarct 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 reversal of comorbid BM impairment. Clinical Trial Registrations: URL: http://www.clinicaltrials.gov.

Original languageEnglish (US)
Pages (from-to)867-874
Number of pages8
JournalCirculation research
Volume115
Issue number10
DOIs
StatePublished - Jan 1 2014

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Keywords

  • Angiogenesis effect
  • Blood cells
  • Bone marrow
  • Myocardial infarction
  • Stem cells

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Cogle, C. R., Wise, E., Meacham, A. M., Zierold, C., Traverse, J. H., Henry, T. D., Perin, E. C., Willerson, J. T., Ellis, S. G., Carlson, M., Zhao, D. X. M., Bolli, R., Cooke, J. P., Anwaruddin, S., Bhatnagar, A., Da Graca Cabreira-Hansen, M., Grant, M. B., Lai, D., Moyé, L., ... Taylor, D. A. (2014). 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, 115(10), 867-874. https://doi.org/10.1161/CIRCRESAHA.115.304353