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微囊化表达VEGF165b的HEK293细胞抗血管生成肿瘤治疗潜力的研究

Investigation of antiangiogenic tumor therapy potential of microencapsulated HEK293 VEGF165b producing cells.

作者信息

Afkhami Fatemeh, Durocher Yves, Prakash Satya

机构信息

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.

出版信息

J Biomed Biotechnol. 2010;2010:645610. doi: 10.1155/2010/645610. Epub 2010 Oct 14.

DOI:10.1155/2010/645610
PMID:20976076
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2957143/
Abstract

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.

摘要

为了研究封装的产生VEGF₁₆₅b的HEK293细胞的抗血管生成潜力,将人胚肾293(HEK293)细胞稳定转染以产生VEGF₁₆₅b。然后将它们封装在藻酸盐-聚赖氨酸-藻酸盐(APA)微胶囊中。分析封装细胞的VEGF₁₆₅b生产率和活力,并与未封装的细胞进行比较。结果表明,在整个28天的实验期间,封装的细胞在微胶囊内增殖并保持活力。VEGF₁₆₅b的量从第13天的6.5±1.2μg/ml增加到第16天的13±0.96μg/ml。然后在第28天测量的最后3天期间逐渐下降至5±1.2μg/ml。封装细胞和未封装细胞产生的VEGF₁₆₅b相似。还检查了从封装细胞收获的VEGF₁₆₅b对人脐静脉内皮细胞(HUVECs)增殖的影响。当细胞与VEGF₁₆₅b和2倍VEGF₁₆₅b的混合物或与从封装细胞释放的VEGF₁₆₅b和2倍过量的VEGF₁₆₅b一起孵育时,对HUVECs增殖具有相同的抑制作用。在裸鼠的肿瘤部位皮下注射微封装的产生VEGF₁₆₅b的细胞导致肿瘤周围血管数量减少。

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本文引用的文献

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VEGF 165 b, an antiangiogenic VEGF-A isoform, binds and inhibits bevacizumab treatment in experimental colorectal carcinoma: balance of pro- and antiangiogenic VEGF-A isoforms has implications for therapy.VEGF 165 b是一种抗血管生成的VEGF - A异构体,在实验性结直肠癌中可结合并抑制贝伐单抗治疗:促血管生成和抗血管生成的VEGF - A异构体之间的平衡对治疗具有重要意义。
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