Human-Induced Pluripotent Stem Cells-Derived Corneal Endothelial-Like Cells Promote Corneal Transparency in a Rabbit Model of Bullous Keratopathy

Stem Cells Dev. 2021 Sep 1;30(17):856-864. doi: 10.1089/scd.2020.0205. Epub 2021 Jul 30.

Abstract

The corneal endothelium (CE) is vital for the cornea to maintain its transparency. However, CE dysfunction occurs due to aging, intraocular surgery, trauma, dystrophy, etc. Corneal transplantation is the only method to clinically treat CE dysfunction; however, this treatment strategy faces the disadvantages of a global cornea shortage, graft failure, and severe side effects. There is a recognized need for a substitute for the CE. Stem cells are becoming increasingly common for the treatment of human diseases. In fact, several studies have documented the induction of corneal endothelial-like cells (CECs) from stem cells, but an ideal procedure has not yet been established. Thus, this study aimed at exploring a more efficient and robust differentiation method. We used a modified approach to differentiate induced pluripotent stem cells (iPSCs) into CECs. After the identification of differentiated CECs, the CECs were injected into the anterior chambers of the eyes of a rabbit model of bullous keratopathy. The rabbits were maintained in the eye-down position to ensure that the cells attached to the cornea. The results showed that corneal edema was alleviated in the rabbits injected with CECs compared with that in the rabbits belonging to the control group. This study extends the ability to differentiate iPSCs into CECs and provides a potential strategy for the treatment of reduced visual acuity caused by CE deficiency in the future.

Keywords: bullous keratopathy; corneal endothelium; induced pluripotent stem cells; neural crest; stem cell differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cornea
  • Corneal Diseases* / surgery
  • Corneal Edema* / surgery
  • Corneal Transplantation*
  • Endothelium, Corneal / transplantation
  • Humans
  • Induced Pluripotent Stem Cells*
  • Rabbits