In vitro and in vivo differentiation of human embryonic stem cells into retina-like organs and comparison with that from mouse pluripotent epiblast stem cells

Abstract

Correctly inducing the differentiation of pluripotent hESCs to a specific lineage with high purity is highly desirable for regenerative cell therapy. Our first effort to perform in vitro differentiation of hESCs resulted in a limited recapitulation of the ocular tissue structures. When undifferentiated hESCs were placed in vivo into the ocular tissue, in this case into the vitreous cavity, 3-dimensional retina-like structures reminiscent of the invagination of the optic vesicle were generated. Immunohistochemical analysis confirmed the presence of both a neural retina-like cell layer and a retinal pigmented epithelium-like cell layer, possibly equivalent to the developing E12.5 mouse retina. Furthermore, mouse epiblast-derived stem cells, which are reported to share some characteristics with hESCs, but not with mouse ESCs, also generated retinal anlage-like structures in vivo. hESC-derived retina-like structures present a novel therapeutic possibility for retinal diseases and also provide a novel experimental system to study early human eye development.