Human ESC–derived retinal epithelial cell sheets potentiate rescue of photoreceptor cell loss in rats with retinal degeneration

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Science Translational Medicine  20 Dec 2017:
Vol. 9, Issue 421, eaai7471
DOI: 10.1126/scitranslmed.aai7471

Growing cell sheets for retinal transplantation

Loss of retinal pigment epithelial (RPE) cells is responsible for severe vision impairments in retinal degenerative disorders, such as retinitis pigmentosa. Stem cell–derived RPE cells have shown promise as a cell therapy for treating retinal degeneration in preclinical studies, but long-term positive outcomes require efficient engraftment and survival of the transplanted cells. Taking a step in this direction, Ben M’Barek et al. have developed a tissue-engineered product comprising human embryonic stem cell (hESC)–derived RPE cells that were grown as sheets on a biological scaffold. Transplantation of these hESC-RPE cell sheets into a rat model of retinal degeneration resulted in greater cell engraftment and survival and improved visual acuity compared to hESC-RPE cells transplanted as cell suspensions. These tissue-engineered cell sheets may improve the efficacy of cell therapy for treating retinal degenerative diseases.


Replacing defective retinal pigment epithelial (RPE) cells with those derived from human embryonic stem cells (hESCs) or human-induced pluripotent stem cells (hiPSCs) is a potential strategy for treating retinal degenerative diseases. Early clinical trials have demonstrated that hESC-derived or hiPSC-derived RPE cells can be delivered safely as a suspension to the human eye. The next step is transplantation of hESC/hiPSC-derived RPE cells as cell sheets that are more physiological. We have developed a tissue-engineered product consisting of hESC-derived RPE cells grown as sheets on human amniotic membrane as a biocompatible substrate. We established a surgical approach to engraft this tissue-engineered product into the subretinal space of the eyes of rats with photoreceptor cell loss. We show that transplantation of the hESC-RPE cell sheets grown on a human amniotic membrane scaffold resulted in rescue of photoreceptor cell death and improved visual acuity in rats with retinal degeneration compared to hESC-RPE cells injected as a cell suspension. These results suggest that tissue-engineered hESC-RPE cell sheets produced under good manufacturing practice conditions may be a useful approach for treating diseases of retinal degeneration.

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