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(Circulation Research. 2008;103:203.)
© 2008 American Heart Association, Inc.

Integrative Physiology

Interleukin-10 From Transplanted Bone Marrow Mononuclear Cells Contributes to Cardiac Protection After Myocardial Infarction

Jana S. Burchfield, Masayoshi Iwasaki, Masamichi Koyanagi, Carmen Urbich, Nadia Rosenthal, Andreas M. Zeiher, Stefanie Dimmeler

From the Department of Molecular Cardiology, Internal Medicine III, J. W. Goethe University, Frankfurt, Germany (J.S.B., M.I., M.K., C.U., A.M.Z., S.D.); and the European Molecular Biology Laboratory (EMBL), Mouse Biology Unit, Rome, Italy (N.R.).

Correspondence to Stefanie Dimmeler, PhD, Department of Molecular Cardiology, Internal Medicine III, University of Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany. E-mail dimmeler{at}em.uni-frankfurt.de

Bone marrow mononuclear cells (BM-MNCs) have successfully been used as a therapy for the improvement of left ventricular (LV) function after myocardial infarction (MI). It has been suggested that paracrine factors from BM-MNCs may be a key mechanism mediating cardiac protection. We previously performed microarray analysis and found that the pleiotropic cytokine interleukin (IL)-10 was highly upregulated in human progenitor cells in comparison with adult endothelial cells and CD14⁺ cells. Moreover, BM-MNCs secrete significant amounts of IL-10, and IL-10 could be detected from progenitor cells transplanted in infarcted mouse hearts. Specifically, intramyocardial injection of wild-type BM-MNCs led to a significant decrease in LV end-diastolic pressure (LVEDP) and LV end-systolic volume (LVESV) compared to hearts injected with either diluent or IL-10 knock-out BM-MNCs. Furthermore, intramyocardial injection of wild-type BM-MNCs led to a significant increase in stroke volume (SV) and rate of the development of pressure over time (+dP/dt) compared to hearts injected with either diluent or IL-10 knock-out BM-MNCs. The IL-10–dependent improvement provided by transplanted cells was not caused by reduced infarct size, neutrophil infiltration, or capillary density, but rather was associated with decreased T lymphocyte accumulation, reactive hypertrophy, and myocardial collagen deposition. These results suggest that BM-MNCs mediate cardiac protection after myocardial infarction and this is, at least in part, dependent on IL-10.

Key Words: acute myocardial infarction • remodeling • growth factors/cytokines • cell therapy

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