Abstract
This chapter summarizes the design and outcomes of the first clinical trials of human embryonic stem cell (hESC)-derived retinal pigment epithelial (RPE) cell transplantation therapy for retinal regeneration. The MA09-(hESC) line was derived from the blastomere stage of a donated embryo and expanded on mitotically inactivated mouse embryonic fibroblasts according to the Good Manufacturing Practices. The MA09-hRPE cells were then tested for safety and terminal differentiation into mature RPE cells by gene expression analysis, karyotyping, phagocytosis assay, and differentiation and purity evaluation by way of morphology, quantitative polymerase chain reaction, and quantitative immune staining for RPE and hESC markers. Two phase I/II open-label, multicenter, prospective clinical trials investigating the safety of subretinal injection of hESC-derived RPE cell suspension in patients with end-stage atrophic age-related macular degeneration (AMD) and Stargardt macular dystrophy (SMD) were performed. The visual outcomes were encouraging with some patients gaining more than ten letters in both groups; however, these results must be tempered by the lack of a control group, poor initial visual acuity, short follow-up, and limited number of patients. Thirteen of eighteen patients (72%) developed areas of increased subretinal pigmentation, some of which appeared to correlate to hyper-reflective bands on optical coherence tomography. The transplanted cells showed no evidence of tumor formation, adverse preretinal RPE cell engraftment, or clinically apparent rejection. Aside from a case of acute postoperative endophthalmitis, there were no issues with the surgical procedure itself. These promising results suggest that hESC-derived RPE cells could represent a novel treatment paradigm for retinal degenerations hallmarked by tissue loss or dysfunction.