Toward the generation of rod and cone photoreceptors from mouse, monkey and human embryonic stem cells

Fumitaka Osakada, Hanako Ikeda, Michiko Mandai, Takafumi Wataya, Kiichi Watanabe, Nagahisa Yoshimura, Akiori Akaike, Yoshiki Sasai, Masayo Takahashi

Research output: Contribution to journalArticlepeer-review

495 Citations (Scopus)

Abstract

We previously reported the differentiation of mouse embryonic stem (ES) cells into retinal progenitors. However, these progenitors rarely differentiate into photoreceptors unless they are cultured with embryonic retinal tissues. Here we show the in vitro generation of putative rod and cone photoreceptors from mouse, monkey and human ES cells by stepwise treatments under defined culture conditions, in the absence of retinal tissues. With mouse ES cells, Crx+ photoreceptor precursors were induced from Rx+ retinal progenitors by treatment with a Notch signal inhibitor. Further application of fibroblast growth factors, Shh, taurine and retinoic acid yielded a greater number of rhodopsin+ rod photoreceptors, in addition to default cone production. With monkey and human ES cells, feeder- and serum-free suspension culture combined with Wnt and Nodal inhibitors induced differentiation of Rx+ or Mitf+ retinal progenitors, which produced retinal pigment epithelial cells. Subsequent treatment with retinoic acid and taurine induced photoreceptor differentiation. These findings may facilitate the development of human ES cell-based transplantation therapies for retinal diseases.

Original languageEnglish
Pages (from-to)215-224
Number of pages10
JournalNature Biotechnology
Volume26
Issue number2
DOIs
Publication statusPublished - 02-2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Medicine
  • Biomedical Engineering

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