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Ramiro Ribeiro, Michael Koss, Bruno Diniz, Rodrigo Brantfernandes, Laura Liu, Padmaja Thomas, Biju Thomas, Gerald Chader, David Hinton, Mark Humayun; Long-term Efficacy and Safety of an RPE Cell Monolayer Derived From Human Embryonic Stem Cells Implanted into the Subretinal Space of the RCS Rat. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2219.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate long term safety and efficacy of RPE derived from human embryonic stem cells (hESCs) seeded as a monolayer on a sub-micron parylene-C membrane implanted into the subretinal space of the dystrophic Royal College of Surgeons (RCS) rat
All experiments were performed in compliance with the ARVO Statement on the Use of Animals Care and Use Committee (IACUC) at the University of Southern California. A mesh-supported submicron parylene-C membrane was seeded with hESC-RPE, differentiated into a polarized monolayer, and implanted in the RCS rats (n=20). A sham group (n=10) received the implant of the parylene membrane without cells. The fellow eye (n=30) served as the untreated control group. Visual behavior was measured at different time points using optokinetic (OKN) head tracking. Eyes were processed for histology at P150, P210, P270 and P390. An experienced pathologist analyzed the retinal morphology. The outer nuclear layer (ONL) was quantified using an Aperio scan scope. Characterization of human RPE was performed using a human-specific cell surface marker (anti-TRA-185) and anti-RPE65. Rhodopsin and cone markers were used to demonstrate photoreceptor rescue
Animals implanted with hESC-RPE performed significantly better (p<0.05) than the sham and control groups on the OKN behavioral test after P63. For example, at P77 the head tracking results in the hESC-RPE implanted group averaged 16.07 ± 0.33 seconds, the sham group 11 ± 0.84 seconds and the non-operated group 8.30 ± 0.16 seconds. Histologic studies did not show cell migration off the membrane or tumor formation. Nuclei in the ONLs were in higher number in the implanted (183 ± 16 cells) than the non-treated (15 ± 6 cells) eye at P150. RPE65, TRA-185, rhodopsin and cone markers were positive in the implant site of the majority of the rats implanted with hESC-RPE but not in control/sham cases receiving no hESC-RPE cells
The transplantation of an hESC-RPE monolayer seeded on a membrane was safely performed and was associated with a better long term functional outcome than with the sham and control groups
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