OpRegen retinal pigment epithelial (RPE) cell therapy engrafts within the RPE of Gottingen mini-pigs by 4-weeks post-administration via subretinal delivery

Abstract

Purpose : To evaluate the survival and the distribution of OpRegen (a suspension of human allogeneic RPE cells) 4 weeks post-administration via pars plana vitrectomy with subretinal delivery in Gottingen minipigs.

Methods : 5-6 month old, male, Gottingen minipigs (n=8, 11.2-14.6 kg) were subretinally administered 40-100 µL OpRegen suspension formulations (100,000-200,000 cells/eye) to both eyes via pars plana vitrectomy using varying surgical instrumentation and methodology as part of a surgical development study. One eye was not dosed due to a retinal detachment during vitrectomy. Animals were immunosuppressed to prevent rejection of xenotransplanted cells, then monitored for 4 weeks after surgery. OpRegen was injected into the subretinal space without attempt to disrupt or ablate the native porcine RPE. OpRegen presence, survival, and differentiation were evaluated by a combination of histomorphological assessment [Hematoxylin and Eosin (H&E)] and immunohistochemistry (IHC) phenotyping [ku80 (human origin) dual staining w/ PMEL17 (differentiated RPE)]. Sections from 7-levels per eye were evaluated including the optic nerve, visual streak, and administration site. All slides were evaluated by board-certified veterinary pathologists.

Results : OpRegen RPE cells organized as a monolayer, and integrated into native RPE were identified by IHC (ku80+ cells). OpRegen was observed in the subretinal space of 8/15 eyes and in 6 of these 8 eyes, OpRegen integrated into the minipig RPE as a monolayer. These cells were indistinguishable from the native RPE on H&E and were ku80+ (indicating human origin [e.g., OpRegen]) and PMEL17+ (retention of RPE features).

Conclusions : Engraftment of OpRegen was demonstrated in this large animal surgical model. The similar size of the minipig eye compared to human eyes provides a useful model for evaluating surgical procedures intended for human use.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.

 

Left: Procedure site, OpRegen administration. Note preservation of overlying retinal morphology (H&E). Right and Inset: IHC demonstrating integration of OpRegen as a monolayer within the procedure site (purple; ku80 e.g., OpRegen).

 

Regionally extensive integration of OpRegen cells (purple: ku80; yellow: PMEL17) as a monolayer within the RPE of a Gottingen minipig.