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W. Tao, P. Stabilia, D. Litvak, J. Mills, A. Lee, C. McGovern, J. Lydon, R. Wenthold, K. Kauper; Development of a Micronized Encapsulated Cell Technology (ECT) Device Capable of Producing Therapeutic Proteins to the Vitreous . Invest. Ophthalmol. Vis. Sci. 2005;46(13):497.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To evaluate the feasibility of manufacturing and implanting a "micronized" encapsulation cell technology (ECT) device capable of producing sufficient and consistent levels of protein therapeutics to treat retinal diseases developed in rodent models. Methods: Devices were fabricated using dialysis membranes with dimensions of 200 micron diameters and overall implant lengths of 1 millimeter. Total displaced volume of devices was less than 0.3 microliters, a reduction compared to the current human clinical ECT devices of more than 200 percent volume. Membranes were manufactured with either polysulfone/polyvinyl pyrrolidone or polyimide. Various cell scaffolding matrices were investigated to induce cell attachment, cell growth, and sustain viability. Scaffolding matrices included: alginate cross–linked with CaCl, Matrigel, Purapeptide, and non–degradable microspheres with and without fibronectin. Encapsulation of a cell suspension without a matrix was also investigated. Combinations of membrane and scaffolding were evaluated and devices encapsulated with NTC–201 cells producing either CNTF or IL–10. Protein secretion over the course of the in vitro evaluation period was quantified by ELISA. Encapsulated cell viability was evaluated using a DNA assay to determine total cell number, nuclear fluorescent labeling of live cells, apoptotic cytohistochemistry and histomorphological examination of sectioned devices. Additionally, devices were implanted in the mouse vitreous and clinically evaluated over the course of one month. Results: Polyimide membranes using polystyrene microspheres as a cell scaffold resulted in the greatest levels of protein production over the course of a 1–month evaluation period. Cell viability within this group of micronized devices remained healthy with no evidence of necrosis or apoptosis. Clinical evaluation of devices implanted into the vitreous of mice showed that the devices remained in a fixed position, avoiding contact with the large mouse lens and with no adverse findings reported during the course of the 1–month follow–up period. Conclusions: Based upon our initial investigation it appears that manufacture and maintenance of micronized ECT devices capable of producing sustained levels of protein are possible and that these devices are well tolerated in the mouse vitreous.
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