June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Long Term Efficacy of Xeno-free hESC-derived RPE Cells Following Transplantation into Royal College of Surgeons Rats
Author Affiliations & Notes
  • Michael D Andrews
    Casey Eye Institute, OHSU, Portland, OR
  • Jonathan Stoddard
    Department of Neuroscience, Oregon National Primate Research Center, Portland, OR
  • Nir Netzer
    Cell Cure Neurosciences Ltd., Jersalem, Israel
  • Osnat Bohana-Kashtan
    Cell Cure Neurosciences Ltd., Jersalem, Israel
  • Charles Irving
    Cell Cure Neurosciences Ltd., Jersalem, Israel
  • Neelay Pandit
    Casey Eye Institute, OHSU, Portland, OR
  • Eyal Banin
    Ophthalmology, Center for Retinal and Macular Degenerations, Jerusalem, Israel
  • Benjamin Reubinoff
    The Goldyne Savad Institute of Gene Therapy, Sidney and Judy Swartz Embryonic Stem Cell Research Center, Jerusalem, Israel
    The Department of Obstetrics and Gynecology, Sidney and Judy Swartz Embryonic Stem Cell Research Center, Jerusalem, Israel
  • Mark E Pennesi
    Casey Eye Institute, OHSU, Portland, OR
  • Trevor J McGill
    Casey Eye Institute, OHSU, Portland, OR
    Department of Neuroscience, Oregon National Primate Research Center, Portland, OR
  • Footnotes
    Commercial Relationships Michael Andrews, Cell Cure Neurosciences Ltd. (F); Jonathan Stoddard, Cell Cure Neurosciences Ltd. (F); Nir Netzer, Cell Cure Neurosciences Ltd. (E); Osnat Bohana-Kashtan, Cell Cure Neurosciences Ltd. (E); Charles Irving, Cell Cure Neurosciences Ltd. (E); Neelay Pandit, Cell Cure Neurosciences Ltd. (F); Eyal Banin, Cell Cure Neurosciences Ltd. (C); Benjamin Reubinoff, Cell Cure Neurosciences Ltd. (C), Cell Cure Neurosciences Ltd. (F), Cell Cure Neurosciences Ltd. (P); Mark Pennesi, None; Trevor McGill, Cell Cure Neurosciences Ltd. (F)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 1275. doi:
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      Michael D Andrews, Jonathan Stoddard, Nir Netzer, Osnat Bohana-Kashtan, Charles Irving, Neelay Pandit, Eyal Banin, Benjamin Reubinoff, Mark E Pennesi, Trevor J McGill; Long Term Efficacy of Xeno-free hESC-derived RPE Cells Following Transplantation into Royal College of Surgeons Rats. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1275.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: Retinal degenerative diseases (RDD) affect millions of people worldwide resulting in progressive and permanent vision loss. To evaluate long-term efficacy, retinal pigmented epithelial (RPE) cells derived from a xeno-free clinical grade human embryonic stem cell source were transplanted into the sub-retinal space of the Royal College of Surgeons (RCS) rats. Subsequent evaluations included quantification of visual function preservation, an assessment of transplanted cell survival and function (phagocytosis), local migration, and quantification of rod and cone photoreceptor rescue.

Methods: Post-natal day (P) 20-25 RCS rats (n=236) received subretinal injection of a single cell transplant of 25,000 (low), 100,000 (mid), or 200,000 (high) OpRegen RPE cells, BSS+ (vehicle control), or were unoperated controls. Fundus photography was used to confirm successful delivery of cells/vehicle into the subretinal space. Four survival groups were examined P60, P100, P150, and P200. Optomotor tracking and electroretinography (ERG) were used to confirm functional efficacy. Cross-sectional histology and immunohistochemistry were used to confirm structural rescue and transplanted cell survival and function.

Results: Optomotor testing revealed that cell treated eyes outperformed vehicle injected or unoperated eyes at all ages. Both mid and high cell-dosed eyes significantly outperformed the low dose, but were not significantly different from one another. ERG testing revealed select cell treated animals that significantly outperformed control or fellow eyes in both focal and full-field ERGs independent of dose. Cell treated eyes had significantly thicker outer nuclear layers than controls up to P150, however no significant difference was observed at P200. Transplanted OpRegen RPE cells were identified in all age groups, generated a monolayer and demonstrated the ability to phagocytose rat rhodopsin.

Conclusions: When transplanted into the subretinal space of RCS rats, OpRegen RPE cells rescued visual acuity, ERG b-wave amplitudes, and rod and cone photoreceptors within close proximity to the grafted cells. Therefore, OpRegen RPE cells appear to have significant potential for the treatment of human RPE cell disorders such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD).

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