Optimization of microencapsulated recombinant CHO cell growth, endostatin production, and stability of microcapsule in vivo.

Abstract

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.