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JJ Crouzet, E Clérin, PJ Coffey, A Darmon, S Brimicombe-Lefevre, A Zerbib, L Hetherington, L Vignais, S Timsit, M Neuner-Jehle; Cell Therapy: A Cryopreserved Immortalized Human RPE Cell Line Rescues Visual Function in the RCS Rat . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3447.
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Purpose: Neurotech S.A. is developing cell-based therapies for the treatment of ophthalmic disorders with a special interest in retinal degenerations. One of the company's core technologies consists of producing immortalized human retinal pigment epithelium (RPE) cell lines which can be safely used for RPE cell replacement therapies in humans. Such cell lines present many advantages over primary RPE cells; they can be thoroughly characterized and tested for microbiological safety. Moreover, extensive pharmacological studies can be performed on a standardized product that would be used in the clinic. Well-characterized human RPE cell lines have recently been described to be efficient in rescuing photoreceptors in the dystrophic Royal College of Surgeons (RCS) rat model when they were freshly harvested from culturesa. Here we investigated whether thawed immortalized human RPE cells (NTC-200 cells) could be used instead of cells directly harvested from cultures. Methods: Three-week-old pigmented dystrophic RCS rats were treated under general anesthesiab by a unilateral injection of 2x105 thawed NTC-200 cells (2 µl) into the temporal superior subretinal space using a trans-scleral approach. Sham-treated dystrophic RCS rats received a unilateral subretinal injection of 2 µl graft medium. At the age of 8 and 12 weeks, all treated rats were subjected to optokinetic reflex testings using the spatial grating frequency of 0.5 cycles/degreec. At the age of 12 weeks, all treated rats were sacrificed for histology and photoreceptor nuclei counting. Results: A significant preservation of visual function was found in animals grafted with thawed NTC-200 cells. Conclusion: The presented results contribute to the concept of using cryopreserved immortalized human RPE cell lines as a bioactive clinical product. a Lund et al. (2001) Proc. Natl. Acad. Sci. USA 98(17):9942-9947, Coffey et al. (2001) Nat. Neurosci., in press. b All animal experiment procedures conform to NIH guidelines. c Cowey & Franzini (1979) Exp. Brain Res. 35,443-455.
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