Review: Corneal endothelial cell derivation methods from ES/iPS cells

Shin Hatou, Shigeto Shimmura

Research output: Contribution to journalReview articlepeer-review

19 Citations (Scopus)


Globally, approximately 12.7 million people are awaiting a transplantation, while only 185,000 cases of corneal transplantation are performed in a year. Corneal endothelial dysfunction (bullous keratopathy) due to Fuchs' corneal endothelial dystrophy, or insults associated with intraocular surgeries, shared half of all indications for corneal transplantation. Regenerative therapy for corneal endothelium independent of eye bank eyes has great importance to solve the large supply-demand mismatching in corneal transplantation and reduce the number of worldwide corneal blindness. If corneal endothelial cells could be derived from ES or iPS cells, these stem cells would be the ideal cell source for cell therapy treatment of bullous keratopathy. Four representative corneal endothelial cell derivation methods were reviewed. Components in earlier methods included lens epithelial cell-conditioned medium or fetal bovine serum, but the methods have been improved and materials have been chemically more defined over the years. Conditioned medium or serum is replaced to recombinant proteins and small molecule compounds. These improvements enabled to open the corneal endothelial developmental mechanisms, in which epithelial-mesenchymal and mesenchymal-endothelial transition by TGF beta, BMP, and Wnt signaling have important roles. The protocols are gradually approaching clinical application; however, proof of efficacy and safety of the cells by adequate animal models are the challenges for the future.

Original languageEnglish
Article number19
JournalInflammation and Regeneration
Issue number1
Publication statusPublished - 2019 Oct 3


  • Bone morphogenetic protein
  • Embryonic stem cells
  • Epithelial-mesenchymal transition
  • Induced pluripotent stem cells
  • Neural crest cells
  • Transforming growth factor beta
  • Wnt

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Cell Biology


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