Editors' ChoiceRetinal Disease

What’s old is new again: Autologous stem cell transplant for AMD

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Science Translational Medicine  26 Apr 2017:
Vol. 9, Issue 387, eaan2783
DOI: 10.1126/scitranslmed.aan2783

Abstract

Transplanted RPE cells derived from induced pluripotent stem cells maintained vision and were well tolerated in a patient with age-related macular degeneration.

Wet age-related macular degeneration (wet AMD) is a common form of retinal disease that can have a profound impact on quality of life. In patients with wet AMD, retinal pigment epithelial (RPE) cells, which provide essential support to retinal neurons, are disrupted by the formation of neovascular growths under the retina. Currently available treatments for wet AMD involve repeated intraocular injections of anti-VEGF compounds to slow the ectopic growth of blood vessels and do not treat the underlying condition or repair damaged retinal cells.

Transplantation of RPE cells holds promise for treating wet AMD, although previous approaches using grafts derived from embryonic stem cells have encountered problems with graft rejection and side effects from immunosuppression. These results suggest that autologous transplantation, in which a patient’s own cells are used as a source for new RPE, might provide therapeutic benefit while avoiding an immune response.

In this study, Mandai et al.show the feasibility of transplanting a sheet of RPE cells differentiated from autologous dermal fibroblast-derived induced pluripotent stem cells (iPSCs) and demonstrate in a single patient that the graft was well tolerated. A year after the procedure, the transplanted sheet of RPE cells was maintained, the tissue had uncurled into a flattened monolayer surrounded by functional retinal cells, and visual acuity had not changed. Before transplantation, the iPSC-derived cells were thoroughly screened for any acquired mutations and were characterized according to their DNA methylation and gene expression profiles. A second patient initially selected for this clinical study did not receive the treatment after testing revealed several DNA deletions in the iPSC-derived RPE cell preparation.

Although the authors caution that their findings are from a single patient and cannot be extrapolated without repeated testing in additional patients, it is notable that the transplant was well tolerated, that the vision in the patient receiving the transplant remained constant, and that the engrafted cells survived with no sign of tumor formation. Further testing of retinal function in the area of the transplant, as well as data from additional patients, will be important for better understanding the benefit derived from this approach.

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