Transplantation of Induced Stem Cell–Derived Retinal Cells in AMD
New England Journal of Medicine
Mandai et al. conducted a feasibility study in which retinal pigment epithelial (RPE) cells, prepared from autologous induced pluripotent stem cells (iPSCs), were transplanted into the right eye of a patient with age-related macular degeneration (AMD). One year postoperatively, the authors determined that the patient had an intact graft, stable visual acuity, and persistent cystoid macular edema (CME).
The patient was a 77-year-old Japanese woman with bilateral neovascular AMD (subtype: polypoidal choroidal vasculopathy) and progressive loss of visual acuity. Preoperative findings included CME, a fibrotic neovascular membrane with polyps, and a large mass under the macula. (A second patient was enrolled in the study but declined to undergo transplantation.)
Skin fibroblasts from the patient were reprogrammed to iPSCs and then were differentiated into RPE cells. This cell type was validated with sequencing and methylation profiling of the whole genome and with gene expression analyses. Protein coding regions were found to be free of large de novo insertions, deletions, and copy-number variations. No known cancer driver mutations were detected. Absence of tumorigenic potential was confirmed by injecting the RPE cells into immunodeficient mice.
The patient underwent removal of the neovascular membrane and transplantation of a sheet of RPE cells (1.3 mm × 3.0 mm) under the fovea of the right eye. CME resolved immediately after surgery but recurred 4 weeks later and persisted during follow-up, despite treatment with glucocorticoid eyedrops. Although the graft margins initially appeared curled, they flattened gradually over 8 weeks.
One year postoperatively, there was no sign of graft rejection or recurrence of the neovascular membrane. According to optical coherence tomography, the outer nuclear layer was retained on the graft sheet, and the external limiting membrane and choroid space were intact. Microperimetry indicated that the graft was functional but fixation was unstable. Visual acuity neither improved nor declined during follow-up (without additional treatment). The investigators concluded that transplantation of RPE cells was safe and feasible for this patient.
The original article can be found here.