HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Personal Folders Download to citation manager Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lai, V. K. Articles by Galiñanes, M. Search for Related Content PubMed Articles by Lai, V. K. Articles by Galiñanes, M. Related Collections Cardiac - physiology Molecular biology Myocardial protection

J Thorac Cardiovasc Surg 2009;138:1400-1408
© 2009 The American Association for Thoracic Surgery

Evolving Technology/Basic Science

Bone marrow cell–induced protection of the human myocardium: Characterization and mechanism of action

Cardiac Surgery Unit, Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom

Received for publication March 17, 2009; revisions received June 8, 2009; accepted for publication July 6, 2009.

^_* Address for reprints: Manuel Galiñanes, MD, PhD, FRCS, Cardiac Surgery Unit, Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital (Clinical Science Wing), LE3 9QP Leicester, United Kingdom. (Email: mg50{at}le.ac.uk).

Objectives: The mechanism of the putative beneficial effect of myocardial transplantation of bone marrow cells remains unclear. We studied the protective properties of bone marrow cells on the human myocardium and investigated the underlying mechanism.

Methods: Bone marrow cells and the right atrial appendage were obtained from patients undergoing elective cardiac surgery. Myocardial slices were subjected to 90 minutes of simulated ischemia/120 minutes of reoxygenation at 37°C following various protocols. Tissue injury was assessed by creatine kinase released into the media during the reoxygenation period, and myocardial necrosis and apoptosis were determined by propidium iodide and terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling (percent of aerobic control).

Results: Autologous unfractionated bone marrow cells significantly reduced myocardial injury. Maximal protection was obtained with 5 x 10⁶ autologous cells (1.5 x 10⁵ cells/mg wet myocardium) that caused a reduction in creatine kinase release and cell death by necrosis and apoptosis of 70% to 80%. Allogenic bone marrow cells were as protective as the autologous cells and their effect was unaffected by prior frozen storage or culturing. Similar myocardial protection was also attained when bone marrow cells were present only before or during ischemia, or during reoxygenation, a benefit that was comparable with that of ischemic preconditioning. Conditioned media by the bone marrow cells was sufficient to induce protection, which was abolished by the selective insulin-like growth factor-1 receptor blocker PQ401.

Conclusions: Bone marrow cells possess potent myocardial protective properties that are triggered by a secreted factor or factors and mediated by insulin-like growth factor-1 receptor. These results have important clinical implications for the therapeutic use of bone marrow cells in ischemic heart disease and for the design of future clinical studies.

This article has been cited by other articles:

				J. L. Herrmann, A. M. Abarbanell, Y. Wang, B. R. Weil, J. A. Poynter, M. C. Manukyan, and D. R. Meldrum Transforming Growth Factor-{alpha} Enhances Stem Cell-Mediated Postischemic Myocardial Protection Ann. Thorac. Surg., November 1, 2011; 92(5): 1719 - 1725. [Abstract] [Full Text] [PDF]

				G. M. Ellison, D. Torella, S. Dellegrottaglie, C. Perez-Martinez, A. Perez de Prado, C. Vicinanza, S. Purushothaman, V. Galuppo, C. Iaconetti, C. D. Waring, et al. Endogenous Cardiac Stem Cell Activation by Insulin-Like Growth Factor-1/Hepatocyte Growth Factor Intracoronary Injection Fosters Survival and Regeneration of the Infarcted Pig Heart J. Am. Coll. Cardiol., August 23, 2011; 58(9): 977 - 986. [Abstract] [Full Text] [PDF]