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

• Published in: Circulation research Vol. 103; no. 2; pp. 203 - 211
• Main Authors: Burchfield, Jana S, Iwasaki, Masayoshi, Koyanagi, Masamichi, Urbich, Carmen, Rosenthal, Nadia, Zeiher, Andreas M, Dimmeler, Stefanie
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Heart Association, Inc 18.07.2008; Lippincott
• Subjects: Animals; Biological and medical sciences; Bone Marrow Cells - cytology; Bone Marrow Cells - metabolism; Bone Marrow Transplantation; Cardiology. Vascular system; Coronary heart disease; Female; Fundamental and applied biological sciences. Psychology; Heart; Humans; Interleukin-10 - genetics; Interleukin-10 - metabolism; Male; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Microarray Analysis; Myocardial Infarction - metabolism; Myocardial Infarction - prevention & control; Myocardial Infarction - therapy; Myocarditis. Cardiomyopathies; Myocardium - cytology; Myocardium - metabolism; Myocardium - pathology; Neovascularization, Physiologic - physiology; Neutrophils - cytology; T-Lymphocytes - cytology; Ventricular Function, Left - physiology; Ventricular Remodeling - physiology; Vertebrates: cardiovascular system; Myocardial infarction; remodeling; Acute; Cytokine; Cardiovascular disease; Transplantation; Coronary heart disease; Myocardial disease; Vertebrata; Mammalia; Mononuclear cell; growth factors/cytokines; cell therapy; Interleukin 10; Bone marrow; Circulatory system; Protection; acute myocardial infarction; Growth factor
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/CIRCRESAHA.108.178475

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.