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Cited by 426

The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.

In vitro differentiation of retinal cells from human pluripotent stem cells by small-molecule induction

Osakada, Fumitaka, Jin, Zi-Bing, Hirami, Yasuhiko, Ikeda, Hanako, Danjyo, Teruko, Watanabe, Kiichi, Sasai, Yoshiki, Takahashi, Masayo·2009·Journal of Cell Science

Abstract

The use of stem-cell therapy to treat retinal degeneration holds great promise. However, definitive methods of retinal differentiation that do not depend on recombinant proteins produced in animal or Escherichia coli cells have not been devised. Here, we report a defined culture method using low-molecular-mass compounds that induce differentiation of human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells into retinal progenitors, retinal pigment epithelium cells and photoreceptors. The casein kinase I inhibitor CKI-7, the ALK4 inhibitor SB-431542 and the Rho-associated kinase inhibitor Y-27632 in serum-free and feeder-free floating aggregate culture induce retinal progenitors positive for RX, MITF, PAX6 and CHX10. The treatment induces hexagonal pigmented cells that express RPE65 and CRALBP, form ZO1-positive tight junctions and exhibit phagocytic functions. Subsequent treatment with retinoic acid and taurine induces photoreceptors that express recoverin, rhodopsin and genes involved in phototransduction. Both three-factor (OCT3/4, SOX2 and KLF4) and four-factor (OCT3/4, SOX2, KLF4 and MYC) human iPS cells could be successfully differentiated into retinal cells by small-molecule induction. This method provides a solution to the problem of cross-species antigenic contamination in cell-replacement therapy, and is also useful for in vitro modeling of development, disease and drug screening.

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Metadata

Authors
Osakada, F., Jin, Z.-B., Hirami, Y., Ikeda, H., Danjyo, T., Watanabe, K., Sasai, Y., & Takahashi, M.
Venue
Journal of Cell Science
Published
2009-09-01
Volume
122
Issue
17
Pages
3169-3179
ISSN
  • 0021-9533 (ISSN-L)
  • 1477-9137
OpenAlex
W2146078700
Cited by
426
References
11
FWCI
14.04
Type
journal article
Language
en
Open access
closed

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CoChat. (2026). Citation check: In vitro differentiation of retinal cells from human pluripotent stem cells by small-molecule induction. https://app.cochat.ai/papers/10.1242/jcs.050393
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Osakada, F., Jin, Z.-B., Hirami, Y., Ikeda, H., Danjyo, T., Watanabe, K., Sasai, Y., & Takahashi, M. (2009). In vitro differentiation of retinal cells from human pluripotent stem cells by small-molecule induction. Journal of Cell Science. https://doi.org/10.1242/jcs.050393

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