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H. Aoki, T. Kunisada; In vitro and in vivo Differentiation of Human Embryonic Stem Cells Into Retina-Like Organs and Comparison With Those From Mouse Pluripotent Epiblast Stem Cells. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4813.
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© ARVO (1962-2015); The Authors (2016-present)
Human embryonic stem cells (hESCs) are pluripotent cells that can differentiate in vitro into cells of all 3 germ layers, include ocular tissue, and thus have huge therapeutic potential. Correct induction of the differentiation of hESCs to a specific lineage with high purity is highly desirable for regenerative cell therapy. We aimed at developing a procedure to regenerate retinal structures from hESCs. Also, as a control, we established mouse epiblast-derived stem cells reported to share some characteristics with hESCs and compared their behavior and/or differentiation potential in vivo with those of hESCs.
In vitro differentiation of hESCs into eye-like structures was performed by co-culturing hESCs with the PA6 stromal cell line, as reported previously (Aoki et al. 2008. Graefes Arch Clin Exp Ophthalmol.). We also tested cultivation of hESCs in the adult eye, expecting the in vivo environmental cues to be favorable for eye development, since we had earlier found that the developing chick eye is suitable for the development of transplanted retinal and lens cell (Aoki et al. 2006. Exp Eye Res.).
Although we could induce some retinal cells and observed a limited recapitulation of the 3-dimensional structure of ocular tissue in vitro, the efficiency and total number of these cells in the cultures were very low and disadvantageous for further analysis. On the other hand, in vivo differentiation of hESCs allowed us to efficiently induce 3-dimensional eye-like structures. These eye-like structures formed in vivo were reminiscent of the invagination of the optic vesicle to form the optic cup. Immunohistochemical analysis showed the presence of both a neural retina-like layer and a retinal pigmented epithelium-like layer as seen in the optic cup during embryogenesis. Furthermore, mouse epiblast-derived stem cells also generated retinal anlage-like structures in vivo. On the other hand, mouse ESCs generated only teratomas and never generated eye-like structures in vivo.
Eye-like structures generated from hESCs transplanted into the vitreous cavity suggest novel therapeutic possibilities as well as provide a novel experimental system to study early human eye development.
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