The U.S. Food and Drug Administration recently approved phase I/II clinical trials for embryonic stem (ES) cell-based
retinal pigmented epithelium (RPE)
transplantation, but this allograft
transplantation requires lifelong immunosuppressive therapy. Autografts from patient-specific induced pluripotent stem (iPS) cells offer an alternative
solution to this problem. However, more data are required to establish the safety and efficacy of iPS
transplantation in animal models before moving iPS
therapy into clinical trials. This study examines the efficacy of iPS
transplantation in restoring functional vision in Rpe65(rd12)/Rpe65(rd12) mice, a clinically relevant model of
retinitis pigmentosa (RP). Human iPS cells were differentiated into morphologically and functionally RPE-like tissue. Quantitative real-time polymerase chain reaction (RT-PCR) and immunoblots confirmed RPE fate. The iPS-derived RPE cells were injected into the subretinal space of Rpe65(rd12)/Rpe65(rd12) mice at 2 d postnatally. After
transplantation, the long-term surviving iPS-derived RPE graft colocalized with the host native RPE cells and assimilated into the host retina without disruption. None of the mice receiving transplants developed
tumors over their lifetimes. Furthermore, electroretinogram, a standard method for measuring efficacy in human trials, demonstrated improved visual function in recipients over the lifetime of this RP mouse model. Our study provides the first direct evidence of functional recovery in a clinically relevant model of
retinal degeneration using iPS
transplantation and supports the feasibility of autologous iPS cell
transplantation for
retinal and
macular degenerations featuring significant RPE loss.