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Cahil McGovern, Sandy Sherman, Crystal Cortellessa, Konrad Kauper, Michael Rivera, Melissa Stiles, Suzanna Borges, Vincent Ling, Bruce Bouchard, Weng Tao; Evaluation of Candidate Cell Lines Employed to Deliver Different Antiangiogenic Factors Intraocularly Using Encapsulated Cell Technology. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3230.
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To investigate the in vivo performance of Encapsulated Cell Technology (ECT) devices using different cell lines to deliver antiangiogenic factors for periods up to 3 months.
Cell lines secreting antiangiogenic factors were constructed using NTC-200 cells. Once stable output from cells was established, candidate cell lines were encapsulated with ECT devices. The devices were manufactured using standard protocols and were pulsed for factor production at 1, 2, 4, and 6 weeks post manufacture. The devices were subsequently analyzed for metabolic activity and then subjected to either total DNA or histological analysis. Devices held for approximately 3 weeks were implanted in rabbit eyes. The duration of the implantation period ranged from 1 to 3 months. Explanted devices were pulsed for antiangiogenic factor release and subjected to histological analysis. The vitreous was collected and analyzed for antiangiogenic factor levels. Device performance and levels of antiangiogenic factors in the vitreous were quantified by Elisa. Cell metabolic activity was determined using the CCK-8 assay (Dojindo). Total DNA was determined using the Hoefer DyNA Quant 200 fluorometer. Histological examination of the devices was performed using standard hematoxylin and eosin staining techniques.
In vitro stability: The ECT devices released the desired factors and maintained viable cells during the six week evaluation period. Total DNA analysis of devices showed a consistent number of cells was maintained during the six week testing period and histological analysis of device sections showed a high density of healthy cells distributed throughout the device.In vivo performance: Review of clinical observations showed that devices appeared to be well tolerated during the implantation period. Explanted devices contained healthy cells and released consistent levels of the antiangiogenic factor upon explant at 1 and 3 months. Vitreal samples showed that the level of antiangiogenic factor in the vitreous was maintained throughout the implantation period.
The data suggested that the Encapsulated Cell Technology platform was able to achieve sustained delivery of antiangiogenic factors for periods up to 3 months in rabbits. This technology can deliver other factors for a broad range of indications where long-term treatment is required.
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