Long-term Outcomes of Human Embryonic Stem Cell Derived Retinal Pigment Epithelial Cell Transplantation for Retinal Degeneration from Two Phase I/II Trials



To summarize long-term safety data and clinical outcomes of two prospective phase I/II studies assessing safety and tolerability of human Embryonic Stem Cell (hESC) derived retinal pigment epithelial (MA09-hRPE) cell transplantation in patients with atrophic age-related macular degeneration (AMD) and Stargardt disease (SD).


Visual acuity (VA) and images of patients participating in two phase I/II open-label, multi-center, prospective clinical trials investigating subretinal injection of hESC-derived RPE cell suspension in patients with atrophic AMD and SD were evaluated from baseline to the last study visit. Fundus photos, fluorescein angiograms, optical coherence tomography, fundus autofluorescence, and Goldman visual field tests were analyzed.


Patients with severe vision loss (baseline vision from 20/400 to Count Fingers) due to atrophic AMD (n=10) and SD (n=10) were treated. Mean follow-up is 2.97 years in AMD and 3.14 years in SD arm. No cases of tumor formation, macular edema, secondary glaucoma, retinal detachment, adverse preretinal RPE cell engraftment, vascular occlusion, or obvious rejection have been observed. Fifteen patients (75%) developed increased subretinal pigmentation. Seven eyes with preretinal pigmented cell implantation did not demonstrate contractile membrane formation. Excluding 3 AMD and 6 SD patients who experienced significant cataract progression, mean VA improved by 14.3 letters in the treated and 3.0 letters in the fellow eyes of AMD subjects, and improved by 8.4 letters in the treated eyes but deteriorated by 2.7 letters in the fellow eyes of SD subjects. BCVA improved by ≥15 letters in 2 of 7 (29%) AMD subjects and in 1 of 4 (25%) SD subjects at 24 months. Systemic serious adverse events were attributed to immunosuppressive medications and underlying health status.


These long-term results suggest that hESC-derived RPE cells could provide a safe new source of cells for the treatment of medical conditions caused by tissue loss or dysfunction. Further work to assess efficacy of this treatment modality is warranted.



Ninel Z. Gregori
Miami, FL, United States
Email : ngregori@med.miami.edu
Cell Phone: +13059424052
Work Phone: +13053266312