Zhang Ying, Wang Wei, Xie Yubing, Yu Weiting, Lv Guojun, Guo Xin, Xiong Ying, Ma Xiaojun
Laboratory of Biomedical Material Engineering, Dalian Institute of Chemical Physics, Chinese, Academy of Sciences, Dalian 116023, People's Republic of China.
J Biomed Mater Res B Appl Biomater. 2008 Jan;84(1):79-88. doi: 10.1002/jbm.b.30847.
Microencapsulation of recombinant cells secreting endostatin offers a promising approach to tumor gene therapy in which therapeutic protein is delivered in a sustainable and long-term fashion by encapsulated recombinant cells. However, the studies of cell growth and protein production in vivo are very limited. In this study, the effects of microencapsulation parameters on in vivo cell growth, endostatin production, and microcapsule stability after implantation in the peritoneal cavity of mice were for the first time investigated. Microcapsules with liquid core reached higher cell density and endostatin production at day 18 than microcapsules with solid core. There was no significant difference in stability whether the core of the microcapsule was solid or liquid. Decrease in microcapsule size increased the stability of microcapsule. The microcapsules kept intact in the peritoneal cavity of mice after 36 days of implantation when the microcapsules size was 240 microm in diameter, which gave rise to high endostatin production as well. The optimized microencapsulation conditions for in vivo implantation are liquid core and 240 microm in diameter. This study provides useful information for antiangiogenic gene therapy to tumors using microencapsulated recombinant cells.
分泌内皮抑素的重组细胞微囊化提供了一种很有前景的肿瘤基因治疗方法，其中治疗性蛋白质由微囊化的重组细胞以可持续和长期的方式递送。然而，体内细胞生长和蛋白质产生的研究非常有限。在本研究中，首次研究了微囊化参数对小鼠腹腔内植入后体内细胞生长、内皮抑素产生以及微囊稳定性的影响。与具有实心核的微囊相比，具有液芯的微囊在第18天达到了更高的细胞密度和内皮抑素产量。无论微囊的核是实心还是液体，稳定性都没有显著差异。微囊尺寸减小增加了微囊的稳定性。当微囊直径为240微米时，植入小鼠腹腔36天后微囊保持完整，这也导致了高内皮抑素产量。体内植入的优化微囊化条件是液芯和直径240微米。本研究为使用微囊化重组细胞进行肿瘤抗血管生成基因治疗提供了有用信息。
