Combination of VEGF(165)/Angiopoietin-1 gene and endothelial progenitor cells for therapeutic neovascularization.
Previous studies have established that vascular endothelial growth factor (VEGF), Angiopoietin-1 (Ang1) and endothelial progenitor cells (EPCs) play important roles in neovascularization, suggesting that combination of them would be a promising therapy for ischemic diseases. So we constructed the adeno-associated virus-2 (AAV-2) vectors simultaneously encoding human VEGF(165) and Ang1 (AAV-Ang1/VEGF), and investigated the combination therapeutic effect of AAV-Ang1/VEGF with EPCs in a rabbit ischemic hindlimb model. In the present study we found that AAV-Ang1/VEGF could successfully and efficiently transfer VEGF(165) and Ang1 gene into bone marrow derived EPCs for gene therapy. Combined administration of AAV-Ang1/VEGF with EPCs had higher blood flow recovery, cellularity, capillary density and smooth muscle alpha-actin positive vessel density than administration of either of them alone. Furthermore, the strategy of pre-intramuscular injection of AAV-Ang1/VEGF followed by EPCs transplantation had a higher therapeutic effect than the strategy of transplantation of AAV-Ang1/VEGF transduced EPCs. It seemed that the former strategy may be a promising therapy for ischemic diseases.
Chen
Feng
F
Department of Vascular Surgery, Zhongnan Hospital, Wuhan University, Wuhan 430071, China.
Tan
Zui
Z
Dong
Chang Yuan
CY
Li
Xiong
X
Xie
YouLi
Y
Wu
Yun
Y
Chen
Xiao
X
Guo
ShuFang
S
D042683:Angiopoietin-1 / Q000627:therapeutic use*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D000229:Dependovirus / Q000235:genetics; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000166:cytology*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006614:Hindlimb / Q000098:blood supply / Q000503:physiopathology; D006801:Humans; D007511:Ischemia / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism / Q000503:physiopathology; D018919:Neovascularization, Physiologic; D011817:Rabbits; D012039:Regional Blood Flow; D013234:Stem Cells / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000627:therapeutic use*
C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A