Abstract
Treatment of ischemic heart disease (IHD) remains a worldwide problem. Gene therapy, and recently, cell transplantation, have made desirable progress. A combination of appropriate stem cells and angiogenic genes appears promising in treating IHD. To study the results of angiogenesis and myogenesis induced by transplantation of the adenovirus carrying human vascular endothelial growth factor 165 (Ad-hVEGF(165))-transfected mesenchymal stem cells (MSCs) in IHD compared with direct MSC transplantation or Ad-hVEGF165 delivery. Cultured MSCs were transfected by Ad-hVEGF(165), and secreted VEGF was measured by ELISA in vitro. Ad-hVEGF(165)-transfected MSCs (MSC/VEGF group), MSCs (MSC group), Ad-hVEGF(165) (VEGF group) or a serum-free medium (control group) was injected into syngeneic Wistar rats immediately after left coronary artery occlusion. All cells were marked with CM-DiI (Molecular Probes, USA) before transplantation. One week after treatment, messenger RNA expression of hVEGF(165) in the MSC/VEGF group was found to be significantly higher than in other groups by reverse transcriptase-polymerase chain reaction analysis. One month after cell transplantation, left ventricular (LV) ejection fraction, capillary density of the infarcted region, infarct size and hemodynamic parameters (including LV end-diastolic pressure, LV+dP/dt and LV-dP/dt) were measured and immunohistochemical analysis was performed. A high level of VEGF was expressed by Ad-hVEGF(165)-transfected MSCs. LV ejection fraction, mean capillary density of the infarcted region and hemodynamic parameters were significantly improved in the MSC/VEGF group compared with the MSC group, the VEGF group and the control group (P<0.001 for all). Partly transplanted MSCs showed the cardiomyocyte phenotype, expressed desmin and cardiac troponin T, and resulted in angiogenesis in the ischemic myocardium. However, a few transplanted MSCs incorporated into the vascular structure and most of the new vascular components were host-derived. The combined strategy of MSC transplantation and VEGF gene therapy can produce effective myogenesis and host-derived angiogenesis, resulting in the prevention of progressive heart dysfunction after myocardial infarction.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
