Derivation of Corneal Keratocyte-Like Cells from Human Induced Pluripotent Stem Cells

PLoS One. 2016 Oct 28;11(10):e0165464. doi: 10.1371/journal.pone.0165464. eCollection 2016.

Abstract

Corneal diseases such as keratoconus represent a relatively common disorder in the human population. However, treatment is restricted to corneal transplantation, which only occurs in the most advanced cases. Cell based therapies may offer an alternative approach given that the eye is amenable to such treatments and corneal diseases like keratoconus have been associated specifically with the death of corneal keratocytes. The ability to generate corneal keratocytes in vitro may enable a cell-based therapy to treat patients with keratoconus. Human induced pluripotent stem cells (hiPSCs) offer an abundant supply of cells from which any cell in the body can be derived. In the present study, hiPSCs were successfully differentiated into neural crest cells (NCCs), the embryonic precursor to keratocytes, and then cultured on cadaveric corneal tissue to promote keratocyte differentiation. The hiPSC-derived NCCs were found to migrate into the corneal stroma where they acquired a keratocyte-like morphology and an expression profile similar to corneal keratocytes in vivo. These results indicate that hiPSCs can be used to generate corneal keratocytes in vitro and lay the foundation for using these cells in cornea cell-based therapies.

MeSH terms

  • Cell Culture Techniques
  • Cell Differentiation*
  • Cell Line
  • Collagen / metabolism
  • Corneal Keratocytes / cytology*
  • Corneal Keratocytes / metabolism
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Iris / cytology
  • Neural Crest / cytology
  • Phenotype

Substances

  • Collagen

Grants and funding

The authors received a Hadden Tom Cat Trust Post-Doctoral Fellowship held in the School Of Medicine Fund (grant #9113/370-4211).