Method for differentiation into retinal cells from stem cells

摘要

Disclosed is a method for inducing stem cells to differentiate into retinal cells at high yield within a short period of time, without gene implantation and co-culture with retinal tissues, by implementing a differentiation process similar to the in vivo embryonic development in chemically defined conditions. Also, retinal cells including the photoreceptor cells and their progenitor cells, and various types of other retinal cells, generated according to the method, are disclosed. A composition comprising the retinal cells and a method are provided for treating retinal degeneration-related diseases. The differentiated photoreceptor cells, when transplanted into degenerated or injured retinas, can be engrafted and fused within the retinas to prevent or cure retinal degeneration.

主权项

1. A method for differentiating stem cells into retinal cells, comprising:
(i) inducing stem cells to differentiate into eye field precursors in a form of floating aggregates by culturing stem cells in a medium containing an IGF1R activator, a Wnt signaling pathway inhibitor and a BMP signaling pathway inhibitor; (ii) inducing the eye field precursors of step (i) to differentiate into retinal progenitor cells by culturing the eye field precursors in a medium containing IGF1R activator, a BMP signaling pathway inhibitor, an FGF signaling pathway activator and a Wnt signaling pathway inhibitor; (iii) inducing the retinal progenitor cells of step (ii) to differentiate into neural retinal progenitor cells by culturing the retinal progenitor cells in a medium containing IGF1R activator, a BMP signaling pathway inhibitor, an FGF signaling pathway activator and a Wnt signaling pathway activator; (iv) inducing the neural retinal progenitor cells of step (iii) to differentiate into photoreceptor cell precursors by culturing the neural retinal progenitor cells in a medium containing an IGF1R activator, a Wnt signaling pathway activator and an Shh (sonic hedgehog) signaling pathway activator; and (v) inducing the photoreceptor cell precursors of step (iv) to differentiate into retinal cells, including photoreceptor cells, by culturing the photoreceptor cell precursors in a medium containing an IGF1R activator, a Wnt signaling pathway activator, an Shh signaling pathway activator and RA (retinoic acid).