Angiomyogenesis for cardiac repair using human myoblasts as carriers of human vascular endothelial growth factor.
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.
Haider
Husnain Kh
HKh
National University Medical Institutes, National University of Singapore, 10 Medical Drive, 117597, Singapore.
Ye
Lei
L
Jiang
Shujia
S
Ge
Ruowen
R
Law
Peter K
PK
Chua
Terrance
T
Wong
Phillip
P
Sim
Eugene K W
EK
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
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