Long-term safety and tolerability of subretinal transplantation of embryonic stem cell-derived retinal pigment epithelium in Asian Stargardt disease patients.

BACKGROUND

Although human embryonic stem cells (hESCs) have been considered a potential therapeutic option for regenerative medicine, there are some concerns regarding tumorigenicity, immunogenicity and ethical considerations. Stargardt macular dystrophy (SMD) is the most common form of juvenile macular degeneration that causes early onset blindness. Therapeutic options for SMD remain limited, although several treatment strategies are currently under investigation. Here, we report a 3-year assessment of a phase I clinical trial involving subretinal transplantation of hESC-retinal pigment epithelium (RPE) cells in patients with SMD.

METHODS

This prospective, non-randomised clinical trial included three patients with SMD. All transplant recipients had central visual acuity no better than 20/400. Trans-pars plana vitrectomy was performed in the eye with poorer vision. RPE cells were reconstituted in balanced salt solution plus, then injected into the subretinal space using a semi-automated subretinal injection method.

RESULTS

No serious adverse events occurred throughout the 3-year period following the injection of hESC-RPE cells. The functional and anatomical results were favourable, compared with the natural course of SMD reported in the ProgStar study. One patient showed best-corrected visual acuity improvement, while the other patients had stable best-corrected visual acuity during the 3-year follow-up period.

CONCLUSION

These results suggest the long-term safety, tolerability, and feasibility of subretinal hESC-derived RPE cell transplantation in regenerative medicine.

TRIAL REGISTRATION NUMBER: NCT01625559.