title: Angiomyogenesis for cardiac repair using human myoblasts as carriers of human vascular endothelial growth factor.
abstract: This study investigated the potential of human skeletal myoblast carrying human VEGF(165) for angiomyogenesis for cardiac repair. A porcine heart model of chronic infarction was created in 18 female swine by coronary artery ligation. The animals were randomized into: group 1, DMEM injected ( n=6), group 2, myoblast transplanted ( n=5) and group 3, VEGF(165) myoblast transplanted ( n=7). Three weeks later 5 ml DMEM containing 3x10(8) myoblast carrying exogenous genes were injected into 20 sites in left ventricle intramyocardially in groups 2 and 3. Group 1 animals were injected 5 ml DMEM without cells. Animals were kept on 5 mg/kg cyclosporine per day for 6 weeks. Regional blood flow was measured using fluorescent microspheres. The heart was explanted between 6-12 weeks after transplantation for histological studies. Histological examination showed survival of lac-z expressing myoblasts in host tissue. Capillary density at low power field (x100) was 57.13+/-4.20 in group 3 which was significantly higher than the other groups. Regional blood flow was significantly improved 6 and 12 weeks after transplantation, which was 2.41+/-0.11 and 3.39+/-0.11 ml(-1) min(-1) g(-1), respectively, in group 3. Left ventricular ejection fraction increased from 31.25+/-4.09% to 43.0+/-2.68% at 6 weeks in group 3. Human myoblasts are potential transgene carriers for the myocardium, in addition to strengthening the weakened myocardium through myogenesis.
authors.affiliation: National University Medical Institutes, National University of Singapore, 10 Medical Drive, 117597, Singapore.
authors.forename: Husnain Kh
authors.initials: HKh
authors.lastname: Haider
authors.forename: Lei
authors.initials: L
authors.lastname: Ye
authors.forename: Shujia
authors.initials: S
authors.lastname: Jiang
authors.forename: Ruowen
authors.initials: R
authors.lastname: Ge
authors.forename: Peter K
authors.initials: PK
authors.lastname: Law
authors.forename: Terrance
authors.initials: T
authors.lastname: Chua
authors.forename: Phillip
authors.initials: P
authors.lastname: Wong
authors.forename: Eugene K W
authors.initials: EK
authors.lastname: Sim
mesh_terms: D000199:Actins / Q000032:analysis / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D005169:Factor VIII / Q000032:analysis / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D018014:Gene Transfer Techniques; D006321:Heart / Q000502:physiology; D006801:Humans; D024510:Muscle Development; D032448:Myoblasts, Skeletal / Q000637:transplantation*; D009203:Myocardial Infarction / Q000628:therapy*; D009206:Myocardium / Q000276:immunology / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000032:analysis / Q000378:metabolism; D018919:Neovascularization, Physiologic; D013552:Swine; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism; D016276:Ventricular Function; D014841:von Willebrand Factor / Q000032:analysis / Q000378:metabolism
chemical_list: D000199:Actins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C473097:factor VIII-von Willebrand factor concentrate 8Y; D014841:von Willebrand Factor; D005169:Factor VIII; D018995:Myosin Heavy Chains