We used human angiopoietin-1 (hAng1)-modified mesenchymal stem cells (MSCs) to treat acute myocardial infarction (AMI) in rats. The hAng1 gene was transfected into cultured rat MSCs using an adenoviral vector. Five million hAng-transfected MSCS (MSCAng1) or green fluorescent protein transfected MSCs (MSCGFP) or PBS only (PBS group) were injected intramyocardially into the inbred Lewis rat hearts immediately after myocardial infarction. MSCAng1 survived in the infarcted myocardium, and expressed hAng1 at both mRNA and protein levels. The vascular density was higher in the MSCAng1 and MSCGFP groups than in the PBS group. The measurements of infarcted ventricular wall thickness, infarction area, and left ventricular diameter indicated that heart remodeling was inhibited and heart function was improved in both the MSCAng1 and MSCGFP groups. However, in contrast to the MSCGFP group, the MSCAng1 group showed enhanced angiogenesis and arteriogenesis (by 11-35%), infarction area was reduced by 30% and the left ventricular wall was 46% thicker (P < 0.05). The results indicated that hAngl-modified MSCs improved heart function, followed by angiogenic effects in salvaging ischernic myocardium and reduced cardiac remodeling. (c) 2007 Elsevier Inc. All rights reserved.