Published online before print January 20, 2005, doi: 10.1161/01.ATV.0000156402.52029.ce
© 2005 American Heart Association, Inc.
Vascular Biology |
Mesoangioblasts, Vessel-Associated Multipotent Stem Cells, Repair the Infarcted Heart by Multiple Cellular Mechanisms
A Comparison With Bone Marrow Progenitors, Fibroblasts, and Endothelial Cells
From Stem Cell Research Institute (D.G., A.I., M.S., G.C., G. Cossu), Dibit, H. San Raffaele, Milan; the Department of Cardiovascular Research (L.S., A.B., E.M., E.C., F.F., S.C., R.L.), Istituto Mario Negri, Milan; Firc Institute of Molecular Oncology (L.Z., E.D.), Milan; Laboratory of Vascular Biology (G.B., E.D.), Istituto Mario Negri, Milan; Department of Experimental Medicine (G. Cusella), University of Pavia; Department of Biomolecular & Biotechnological Sciences (E.D.), University of Milan; Department of Histology and Medical Embryology (G. Cossu), University of Rome La Sapienza; and Institute of Cell Biology and Tissue Engineering (G. Cossu), San Raffaele Biomedical Park of Rome, Italy.
Correspondence to Roberto Latini, Department of Cardiovacular Research, Stem Cell Research, Istituto Mario Negri, Dibit, H. San Raffaele Via Eritrea, 62 Via Olgettina, 58 20157, Milan 20132, Milan, Italy. E-mail latini{at}marionegri.it
Objective— To test the potential of mesoangioblasts (Mabs) in reducing postischemic injury in comparison with bone marrow progenitor cells (BMPCs), fibroblasts (Fbs), and embryonic stem cell–derived endothelial cells (ECs), and to identify putative cellular protective mechanisms.
Methods and Results— Cells were injected percutaneously in the left ventricular (LV) chamber of C57BL/6 mice, 3 to 6 hours after coronary ligation, and detected in the hearts 2 days and 6 weeks later. Echocardiographic examinations were performed at 6 weeks. LV dilation was reduced and LV shortening fraction was improved with Mabs and BMPCs but not with ECs and Fbs. Donor cell colonization of the host myocardium was modest and predominantly in the smooth muscle layer of vessels. Capillary density was higher in the peripheral infarct area and apoptotic cardiomyocytes were fewer with Mabs and BMPCs. Mabs and BMPCs, but not Fbs or ECs, promoted survival of cultured cardiocytes under low-oxygen in culture. This activity was present in Mab-conditioned medium and could be replaced by a combination of basic fibroblast growth factor (bFGF), insulin-like growth factor (IGF)-1, and hepatocyte growth factor (HGF), all of which are produced by these cells. Conditioned medium from Mabs, but not from Fbs, stimulated proliferation of smooth muscle cells in vitro.
Conclusions— Mabs appear as effective as BMPCs in reducing postinfarction LV dysfunction, likely through production of antiapoptotic and angiogenic factors.
Mesoangioblasts (Mabs), vessel-associated stem cells, were compared with bone marrow progenitor cells (BMPCs), fibroblasts, and embryonic stem cell-derived endothelial cells in their ability to ameliorate cardiac function after infarction, aiming to identify putative cellular mechanisms. Mabs appeared as effective as BMPCs in reducing postinfarction damage, likely through production of antiapoptotic and angiogenic factors.
Key Words: stem cells • mesoangioblasts • myocardial infarction • angiogenesis • myogenesis
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