BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: D Orlic; J Kajstura; S Chimenti; I Jakoniuk; S M Anderson; B Li; J Pickel; R McKay; B Nadal-Ginard; D M Bodine; A Leri; P Anversa Journal: Nature Date: 2001-04-05 Impact factor: 49.962
Authors: A A Kocher; M D Schuster; M J Szabolcs; S Takuma; D Burkhoff; J Wang; S Homma; N M Edwards; S Itescu Journal: Nat Med Date: 2001-04 Impact factor: 53.440
Authors: Jeremy L Herrmann; Troy A Markel; Aaron M Abarbanell; Brent R Weil; Meijing Wang; Yue Wang; Jiangning Tan; Daniel R Meldrum Journal: Antioxid Redox Signal Date: 2009-08 Impact factor: 8.401