Long-Term Safety and Function of RPE from Human Embryonic Stem Cells in Preclinical Models of Macular Degeneration

Authors


  • Author contributions: B.L.: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing; C.M.: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing; S.W.: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing and final approval of manuscript; S.G.: collection and/or assembly of data, data analysis and interpretation; P.F.: conception; L.L.: conception and design, collection and/or assembly of data, data analysis and interpretation; R. Lanza: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing and final approval of manuscript; R. Lund: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing and final approval of manuscript. B.L., C.M., and S.W. contributed equally to this article.

  • First published online in STEM CELLS EXPRESS June 11, 2009; available online without subscription through the open access option.

Abstract

Assessments of safety and efficacy are crucial before human ESC (hESC) therapies can move into the clinic. Two important early potential hESC applications are the use of retinal pigment epithelium (RPE) for the treatment of age-related macular degeneration and Stargardt disease, an untreatable form of macular dystrophy that leads to early-onset blindness. Here we show long-term functional rescue using hESC-derived RPE in both the RCS rat and Elov14 mouse, which are animal models of retinal degeneration and Stargardt, respectively. Good Manufacturing Practice-compliant hESC-RPE survived subretinal transplantation in RCS rats for prolonged periods (>220 days). The cells sustained visual function and photoreceptor integrity in a dose-dependent fashion without teratoma formation or untoward pathological reactions. Near-normal functional measurements were recorded at >60 days survival in RCS rats. To further address safety concerns, a Good Laboratory Practice-compliant study was carried out in the NIH III immune-deficient mouse model. Long-term data (spanning the life of the animals) showed no gross or microscopic evidence of teratoma/tumor formation after subretinal hESC-RPE transplantation. These results suggest that hESCs could serve as a potentially safe and inexhaustible source of RPE for the efficacious treatment of a range of retinal degenerative diseases. STEM CELLS 2009;27:2126–2135

Ancillary