Effects of direct infusion of bone marrow-derived progenitor cells and indirect mobilization of hematopoietic progenitor cells on atherosclerotic plaque and inflammatory process in atherosclerosis

• Published in: International journal of cardiology Vol. 168; no. 5; pp. 4769 - 4774
• Main Authors: Tousoulis, Dimitris, Briasoulis, Alexandros, Vogiatzi, Georgia, Valatsou, Aggeliki, Kourkouti, Polina, Pantopoulou, Alkistis, Papageorgiou, Nikolaos, Perrea, Despina, Stefanadis, Christodoulos
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 12.10.2013; Elsevier
• Subjects: Animals; Aortic Diseases - pathology; Aortic Diseases - surgery; Atherosclerosis (general aspects, experimental research); Atherosclerosis - complications; Atherosclerosis - pathology; Atherosclerosis - surgery; Atherosclerotic plaque; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cardiovascular; Cell Count; Cells, Cultured; Disease Models, Animal; Follow-Up Studies; Heart; Hematopoietic Stem Cell Transplantation - methods; Hematopoietic Stem Cells - cytology; Immunohistochemistry; Inflammation; Inflammation - etiology; Inflammation - pathology; Inflammation - surgery; Infusions, Intralesional; Ischemia; Medical sciences; Mice; Mice, Inbred C57BL; Plaque, Atherosclerotic - etiology; Plaque, Atherosclerotic - pathology; Plaque, Atherosclerotic - surgery; Progenitor cells; Stem Cells; Treatment Outcome; Inflammation; Ischemia; Atherosclerotic plaque; Progenitor cells; Stem cell; Hematopoietic cell; Cardiovascular disease; Process; Vascular disease; Infusion; Mobilization; Perfusion; Atherosclerosis; Bone marrow; Cardiology; Progenitor cell
• ISSN: 0167-5273; 1874-1754
• DOI: 10.1016/j.ijcard.2013.07.229

Abstract Background We sought to investigate the effects of lin −/sca + cells, endothelial progenitor cells (EPCs) and granulocyte colony-stimulating factor (G-CSF) administration on atherosclerotic plaque progression. Methods Apolipoprotein E-deficient (apoE−/− ) mice were splenectomized and treated with high-cholesterol diet for 6 weeks in order to induce atherosclerotic plaque development. Bone marrow-derived Lin −/sca-1 + cells were isolated and further cultured to early growth endothelial progenitor cells (EPCs). Mice were divided in four groups ( n = 10/group) and received two intravenous injections of 5 × 105 cells (lin −/sca-1 + or EPCs), or granulocyte colony-stimulating factor (G-CSF 100 μg/kg/day) for 7 days or normal saline. The same interventions were administered to animals, which had undergone unilateral hind-limb ischemia. Effects on inflammatory parameters, lesion severity, and atherosclerotic plaque area size were assessed. Results The administration of both G-CSF and progenitor cells significantly decreased the levels of IL-6, 6 weeks after the initiation of treatment. Atherosclerotic lesion area was reduced by G-CSF (atherosclerotic plaque area percentage 22.94% ± 3.68, p = 0.001), by lin −/sca-1 + (23.27% ± 5.98, p = 0.002) and cultured EPCs (23.16 ± 4.86%, p = 0.002) compared to control (32.75% ± 7.05). In the atherosclerotic mice that underwent limb ischemia, the atherosclerotic plaque area, was not significantly different between the treatment groups cultured EPCs-treated mice and the control group ( p = NS, for all). Conclusions Direct infusion of progenitor cells and indirect mobilization of hematopoietic progenitor cells decreased plaque progression and levels of inflammatory molecules in a murine model of atherosclerosis. Treatment with G-CSF, lin −/sca-1 +, or EPCs may exert beneficial effects on vascular inflammation and atherosclerotic plaque progression. However, the effects are diminished in an ischemic setting.