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Articles in PresS, published online ahead of print May 31, 2002
J Appl Physiol, 10.1152/jap.00307.2002
Submitted on April 8, 2002
Accepted on May 29, 2002
1 Department of Medicine, BIDMC-Harvard Medical School, Boston, MA, USA
* To whom correspondence should be addressed. E-mail: yxiao{at}caregroup.harvard.edu.
Despite considerable advances in medicine, the incidence of heart failure remains high in patients after myocardial infarction (MI). This study investigated the effects of transplanted early-differentiated cells (EDCs) from embryonic stem cells (ESCs), with or without transfection of vascular endothelial growth factor (phVEGF165) cDNA, on cardiac function in postinfarcted mice. Cultured mouse EDCs were transfected with green fluorescent protein (GFP) cDNA for identification of engrafts in myocardium. MI in mice was induced by ligation of the left anterior coronary artery and then EDCs (3 x 105 cells) were transplanted into injured myocardium. The MI control group received an equivalent volume of the cellfree medium. Compared to the MI control mice, left ventricular function was significantly improved in the MI mice 6 weeks after transplantation of EDCs alone. Moreover, improvement of heart function was significantly greater in the mice engrafted with EDCs over-expressing VEGF (EDCs-VEGF) than with EDCs alone. Frozen sections of infarcted myocardium with EDCs or EDCs-VEGF transplantation showed GFP-positive tissue. The area with positive immunostaining for cardiac troponin I and 
-myosin heavy chain was larger in injured myocardium with EDCs or EDCs-VEGF transplantation than with cellfree medium injection. Transplantation of EDCs or EDCs-VEGF significantly increased the number of blood vessels in the MI area. However, the EDCs-VEGF group had a significantly higher density of capillaries in MI myocardium than the EDC group. Double staining for GFP and connexin-43 was positive in injured myocardium with EDC transplantation. Our data demonstrate that transplanted EDCs significantly improved cardiac function in infarcted hearts. The observed improvement of cardiac function might result from cardiogenesis and angiogenesis of engrafted cells. This novel synergistic approach may have an important impact on future cell therapy for patients experiencing MI or heart failure.
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