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.

In Vitro Histogenesis of Human Embryonic Stem Cells into Retina Components

“…The formation of three-dimensional structures similar to the retina was previously observed during co-culturing of human ESC with stromal PA-6 cells [2]. Our fi nding suggest that targeted differentiation of human ESC into separate multicomponent tissue complexes similar by their histological and molecular characteristics to eye retina can be attained without co-coulturing of human ESC with other cells.…”

“…Two types of human pluripotent cells are known: embryonic SC (ESC) and induced pluripotent SC [10]. There are reports on the development of ESC differentiation protocols into pigment retinal epithelial cells [1][2][3][4][5] and photoreceptor cells [6,9], but the possibility of controlled differentiation of this three-dimensional and multicomponent tissue remains an open question.…”

Stem Cell Based Therapies for Glaucoma

“…Proof of concept that human ESCs can successfully differentiate into retinal neurons has been provided by xenologous transplantation. Following intravitreal injection into the adult mouse eye, human ESCs formed structures reminiscent of the developing optic cup and expressed markers of a wide range of retinal progenitors and neurons (Aoki et al, 2009). In addition transplanted murine ESCs have been shown to integrate into the inner and outer nuclear as well as the inner plexiform layers of the retinae of host mice with retinal degeneration.…”

Teratoma showing the features of retinal structure: A case of sacrococcygeal teratoma

“…The similarities between the retina-like structure within the teratoma and the normal mammalian retina are investigated with regard to tissue structure and protein expression (5).…”