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Generation of retinal ganglion cells with functional axons from human induced pluripotent stem cells.


ABSTRACT: We generated self-induced retinal ganglion cells (RGCs) with functional axons from human induced pluripotent stem cells. After development of the optic vesicle from the induced stem cell embryoid body in three-dimensional culture, conversion to two-dimensional culture, achieved by supplementation with BDNF, resulted in differentiation of RGCs at a rate of nearly 90% as indicated by a marginal subregion of an extruded clump of cells, suggesting the formation of an optic vesicle. Axons extended radially from the margin of the clump. Induced RGCs expressed specific markers, such as Brn3b and Math5, as assessed using by quantitative PCR and immunohistochemistry. The long, prominent axons contained neurofilaments and tau and exhibited anterograde axonal transport and sodium-dependent action potentials. The ability to generate RGCs with functional axons uniformly and at a high rate may contribute to both basic and clinical science, including embryology, neurology, pathognomy, and treatment of various optic nerve diseases that threaten vision.

SUBMITTER: Tanaka T 

PROVIDER: S-EPMC4322369 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Generation of retinal ganglion cells with functional axons from human induced pluripotent stem cells.

Tanaka Taku T   Yokoi Tadashi T   Tamalu Fuminobu F   Watanabe Shu-Ichi S   Nishina Sachiko S   Azuma Noriyuki N  

Scientific reports 20150210


We generated self-induced retinal ganglion cells (RGCs) with functional axons from human induced pluripotent stem cells. After development of the optic vesicle from the induced stem cell embryoid body in three-dimensional culture, conversion to two-dimensional culture, achieved by supplementation with BDNF, resulted in differentiation of RGCs at a rate of nearly 90% as indicated by a marginal subregion of an extruded clump of cells, suggesting the formation of an optic vesicle. Axons extended ra  ...[more]

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