Pluripotent stem-cell-derived corneal cells

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Corneal dystrophies are the leading cause of corneal transplantations performed in the United States each year. Although keratoplasty has been successful at visual rehabilitation, graft rejection and lack of suitable donor tissue for transplantation are among the obstacles to reduce cornea-related blindness worldwide. As an alternative to donor corneal transplantation for corneal epithelium dysfunction, cultured limbal stem cell (LSC) transplantation has been performed successfully for the treatment of LSC deficiency to replace the degenerated corneal epithelium. Stromal scarring because of trauma, surgery, or infection is responsible for a significant portion of the corneal blindness worldwide. At present, deep anterior lamellar keratoplasty is the only option to treat corneal stromal disease. The therapeutic potential of stromal keratocytes by differentiating adult dental pulp stem cells, human embryonic stem cells (hESCs), and mesenchymal stem cells for corneal stromal dysfunctions have been reported. In contrast to the epithelium, corneal endothelial cells (CECs) have limited proliferative capability in vivo, which is the driving force for efforts to generate CECs from pluripotent stem cells. Several groups used hESCs and induced pluripotent stem cells (iPSCs) to generate CECs and characterized the differentiated CECs through next-generation based RNA-sequencing (RNA-Seq) and mass-spectrometry-based proteome sequencing. We previously reported the generation and proteome profiling of CECs using the peripheral blood mononuclear cell (PBMC)-originated, iPSCs and recently extended our analysis through RNA-Seq-based transcriptome profiling of hESC- and iPSC-derived CECs. As an alternative to donor corneas, multiple therapeutic options for corneal endothelial dysfunction, including cultured CECs and hESC- and iPSC-derived CECs, are currently under investigation. Different preclinical studies demonstrated the regeneration of corneal endothelium following the injection of a cultured and pluripotent stem-cell-derived CECs, in combination with a Rho kinase (ROCK) inhibitor. Recently, a clinical trial using human cultured CECs supplemented with a ROCK inhibitor reported an increased CEC density in 11 patients with bullous keratopathy. In this chapter, we will discuss efforts by various research groups to generate pluripotent stem-cell-derived corneal cells and their possible therapeutic applications in corneal dystrophies.

Original languageEnglish (US)
Title of host publicationStem Cells
Subtitle of host publicationFrom Myth to Reality and Evolving
Publisherde Gruyter
Pages1-13
Number of pages13
ISBN (Electronic)9783110642438
ISBN (Print)9783110642230
DOIs
StatePublished - Jan 1 2019

Keywords

  • Corneal
  • Dystrophies
  • ESCs
  • Eye
  • IPSCs
  • Limbal stem cells
  • Pluripotent

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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