Transplantation of human induced pluripotent stem cells (hiPSC)-derived retinal pigment epithelium (RPE) cell suspension into the subretinal space of a swine model of geographic atrophy (GA).

Abstract

Purpose :
To test feasibility and safety of a subretinal transplant of hiPSC-derived RPE cells into areas of degenerative retina and into their healthy margins in a swine model of GA.

Methods : Well-delimited selective outer retinal atrophy was induced by subretinal injection of NaIO3 in one eye (n=10). Thirty days after, a suspension of hiPSC-derived RPE cells expressing green fluorescent protein (hiPSC-RPE) was injected into the subretinal space, mainly under the retina margins outside the atrophy to evaluate cell implantation. In vivo follow-up was performed by multimodal imaging. Post-mortem retinas were analyzed by immunohistochemistry and histology.

Results : In vitro Differentiated hiPSC-RPE cells expressed specific RPE genes and showed phagocytic ability with a typical epithelial morphology. Sixty percent of the eyes exhibited engrafted hiPSC-RPE cells, forming mature epithelium in normal retina extending towards the border of the atrophy. Histological images suggested certain RPE integration with host photoreceptors, showing phagosomes. Transplanted cells engrafted in the atrophic zone in a patchy distribution but failed to form an epithelial-like layer.

Conclusions : Subretinal injection of hiPSC-derived RPE cells represents a feasible method with a good long-term cell survival at the borders of the atrophy. Histological images suggest iPSC–derived RPE integration and functionality, which might support their use to treat atrophic age related macular degeneration by seeking a supportive housekeeping effect on remnant overwhelmed RPE cells and photoreceptors, in an attempt to improve their survival and decrease the rate of progression of the GA.

This is a 2020 ARVO Annual Meeting abstract.