Transplantation of microencapsulated genetically modified xenogeneic cells augments angiogenesis and improves heart function.
Cell-based gene therapy offers an alternative strategy for therapeutic angiogenesis for the management of myocardial infarction (MI). However, immune rejection poses a significant obstacle to the implantation of genetically engineered allogeneic or xenogeneic cells. In the present study, an ex vivo gene therapy approach utilizing cell microencapsulation was employed to deliver vascular endothelial growth factor (VEGF) to ischemic myocardium. Chinese hamster ovary (CHO) cells were genetically modified to secrete VEGF and enveloped into semipermeable microcapsules. In vitro assay indicated that the microencapsulated engineered CHO cells could secrete VEGF as high as 3852 pg ml(-1) per 48 h at day 8 after encapsulation. Then the microencapsulated CHO cells were implanted into the injured myocardium in a rat MI model, while engineered CHO cells, blank microcapsules and serum-free culture media were implanted as controls. The humoral immunity to xenogeneic CHO cells were evaluated and we found that the titer of anti-CHO antibodies was significantly lower in the microencapsulated CHO transplantation group than the group receiving unencapsulated CHO cells at two weeks after implantation. However, 1 week later, there was almost no difference between these groups. Histology and western blotting confirmed that the microencapsulated CHO cells maintained their original structure and VEGF secretion three weeks after implantation. The capillary density in the treatment region was also significantly higher in the microencapsulated CHO cell group than control groups, which was consistent with gross heart functional improvement. These data suggest that microencapsulated xenogeneic cell-based gene therapy might be a novel approach for therapeutic angiogenesis in ischemic heart disease.
Zhang
H
H
Research Center for Cardiac Regenerative Medicine, The Ministry of Health, Beijing, PR China.
Zhu
S-J
SJ
Wang
W
W
Wei
Y-J
YJ
Hu
S-S
SS
D000818:Animals; D000917:Antibody Formation; D016466:CHO Cells / Q000378:metabolism / Q000637:transplantation*; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D005818:Genetic Engineering; D015316:Genetic Therapy / Q000379:methods*; D007150:Immunohistochemistry; D007267:Injections; D008297:Male; D008863:Microspheres; D009203:Myocardial Infarction / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism; D018919:Neovascularization, Physiologic; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013194:Staining and Labeling; D014162:Transfection / Q000379:methods; D014183:Transplantation, Heterologous; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000235:genetics* / Q000378:metabolism
D042461:Vascular Endothelial Growth Factor A