Human iPSC‐derived RPE cells implantation into minipig eye: Two weeks follow‐up study

Aims/Purpose: Retinal pigment epithelium (RPE) replacement is a very promising cell‐based therapy for retinal degenerative diseases including age‐related macular degeneration (AMD). RPE dysfunction is the main cause of secondary damage to the photoreceptors. We hereby present RPE implantation into the minipig eye with a 2‐week follow‐up. Methods: Cultured human iPSC‐derived RPEs (iRPE) on nanofibrous membranes, with properties very similar to Bruch's membrane, were characterized for expression of differentiation and polarization markers using immunohistochemistry. The implantations of iRPE‐scaffolds were carried out into the minipig eyes using 3‐port pars plana vitrectomy. Due to the xenogeneic transplantation of human cells into minipig eyes, tacrolimus immunosuppression therapy was used. At the 2‐week follow‐up from transplantation, non‐invasive OCT and fundus camera examinations of the implanted iRPE‐scaffolds were performed. Consequently, euthanasia, histological and immunohistochemical investigations of the implanted retina were performed. Results: OCT and fundus camera examinations revealed successfully implanted iRPE‐scaffolds into the subretinal space with a healthy neuroretina above the implant, and healed retinotomy, without immune cell reaction against the implant. Histological and immunohistochemical investigation of the iRPE implants and adjacent retina showed structurally healthy iRPE‐scaffold implant and neuroretinal cells above the implant. Conclusions: RPE cell therapy for replacement of diseased RPEs by ex vivo cultured Ipsc–RPEs on highly permeable nanofibrous membranes supports the survival of adjacent photoreceptors and thus positively affects the structural changes seen in retinal neurodegeneration.