Changing the Face of Modern Medicine: Stem Cells & Gene Therapy, October 18–21, 2016, Florence, Italy

Age-related macular degeneration (AMD) is a medical condition of the eye that results in blurred vision and/or a loss of central vision. The wet form of AMD – caused by abnormal blood vessel growth – is often treated using anti-VEGF medication. This approach can slow deterioration but is unable to treat the cause, or reverse the effects of, retinal pigment epithelium (RPE) atrophy. A regenerative medicine strategy currently being explored is the possibility that healthy RPE tissue could replace defective RPE. Masayo Takahashi from the RIKEN Center for Developmental Biology (Kobe, Japan) presented data on the creation and utilization of RPE cells from inducible pluripotent stem cells (iPSCs) to treat wet AMD. In 2014, Takahashi led a pilot study of the first transplant of human iPSC-derived tissue into a human being. Skin cells taken from a patient suffering from wet-AMD were converted into iPSCs, differentiated into RPE cells and transplanted back into the patient's eye. Importantly, transplanted cells were not rejected and resulted in the stabilization of visual acuity. However, using autologous cells is a costly option and is of limited use to patients with acute ocular diseases. To address these points, Takahashi has explored the therapeutic use of RPE cells from iPSCs derived from human leukocyte antigen (HLA)-matched homozygote donors. When tested in a monkey model, no rejection signs were observed in monkey iPSC-RPE allografts of MHC-matched animal models, whereas immune attacks around the graft were detected in the MHC-mismatched situation. Using an in vitro assay to assess the immune response in a quasi-human context, T cells were unable to respond to human iPSC-RPE cells derived from HLA homozygous donors. This encouraging result indicates that the allogeneic option is viable and should be tested in future clinical trials if the donor and recipient are HLA matched.