Autologous transplantation of EPCs encoding FGF1 gene promotes neovascularization in a porcine model of chronic myocardial ischemia.
OBJECTIVE
The functional impairment of endothelial progenitor cells (EPCs) constitutes an important barrier for therapeutic angiogenesis. Here, we tested the hypotheses that a secreted version of acidic fibroblast growth factor (sp-FGF1) gene transfer may achieve functional improvement of EPCs and that autologous transplantation of sp-FGF1-modified EPCs can facilitate neovascularization in a porcine model of chronic myocardial ischemia.


RESULTS
EPCs were cultured from porcine peripheral blood and transduced with a recombinant adeno-associated virus encoding the sp-FGF1 gene (Td/FGF1-EPC). EPC function was evaluated 3 days after the gene transfer. In vitro, the sp-FGF1-modified EPCs displayed enhanced migration, tube formation and survival. Chronic myocardial ischemia was induced by the placement of an ameroid constrictor around the left circumflex coronary artery (LCx). Four weeks after ameroid placement, coronary angiography was performed and the cells were administered through the stenotic LCx. Myocardial perfusion defects were significantly reduced in animals transplanted with Td/FGF1-EPC compared to animals that received non-transduced EPCs or PBS (P<0.05) as assessed by SPECT 4 weeks after cell transplantation. Furthermore, the vascular density of ischemic myocardium was significantly increased in Td/FGF1-EPC transplanted animals (P<0.05). In addition, FGF1 protein expression was only detected in Td/FGF1-EPC transplanted animals.


CONCLUSIONS
The functional activities of EPCs were enhanced by sp-FGF1 gene transfer. Transplantation of this gene modified EPCs promoted neovascularization in a porcine model of chronic myocardial ischemia, indicating the therapeutic potential of this cell-based gene therapy strategy for the treatment of ischemic diseases.
Chen
Shu-Yan
SY
Department of Cardiology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, No. 1665 Kong Jiang Road, Shanghai 200092, China.
Wang
Fei
F
Yan
Xue-Yun
XY
Zhou
Qing
Q
Ling
Qiang
Q
Ling
Ji-Xian
JX
Rong
Ye-Zhi
YZ
Li
Yi-Gang
YG
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002455:Cell Division; D002465:Cell Movement; D002470:Cell Survival; D002908:Chronic Disease; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000166:cytology*; D016220:Fibroblast Growth Factor 1 / Q000235:genetics*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D008297:Male; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000628:therapy*; D018919:Neovascularization, Physiologic; D033581:Stem Cell Transplantation; D034421:Sus scrofa; D015899:Tomography, Emission-Computed, Single-Photon; D019076:Transgenes / Q000235:genetics; D014182:Transplantation, Autologous
D016220:Fibroblast Growth Factor 1