Investigation of antiangiogenic tumor therapy potential of microencapsulated HEK293 VEGF165b producing cells.
To investigate the antiangiogenic potential of encapsulated VEGF₁₆₅b producing HEK293 cells, Human Embryonic Kidney 293 (HEK293) cells were stably transfected to produce VEGF₁₆₅b. Then they were encapsulated in alginate-polylysine-alginate (APA) microcapsules. VEGF₁₆₅b productivity and viability of encapsulated cells were analyzed and compared with the non-encapsulated cells. Results showed that encapsulated cells proliferated and remained viable within the microcapsules throughout the 28-day period of the experiment. The quantity of VEGF₁₆₅b increased from 6.5 ± 1.2 μg/ml at day 13 to 13 ± 0.96 μg/ml at day 16. Then it gradually dropped to 5 ± 1.2 μg/ml for the last 3 days period as measured at day 28. Production of VEGF₁₆₅b from encapsulated and non-encapsulated cells was similar. The effect of VEGF₁₆₅b harvested from encapsulated cells on Human Umbilical Vein Endothelial cells (HUVECs) proliferation were also examined.The same inhibitory effects on HUVECs proliferation was seen when the cells were incubated with a mixture of VEGF₁₆₅b and a 2-fold VEGF₁₆₅b or with VEGF₁₆₅b and 2-fold excess VEGF₁₆₅b released from encapsulated cells. Subcutaneous injection of microencapsulated VEGF₁₆₅b producing cells in tumor site of nude mice resulted in the reduction of the number of vessels around the tumors.
Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering and Artificial Cells and Organs Research Center, Faculty of Medicine, McGill University, 3775 University Street, Montreal, QC H3A2B4, Canada.
Fatemeh
F
Afkhami
Yves
Y
Durocher
Satya
S
Prakash
D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001681:Biological Assay; D015153:Blotting, Western; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004339:Drug Compounding; D004797:Enzyme-Linked Immunosorbent Assay; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000378:metabolism
D020533:Angiogenesis Inhibitors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A