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

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 suc...

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Bibliographic Details
Published in:PloS one 2016-10, Vol.11 (10), p.e0165464-e0165464
Main Authors: Naylor, Richard W, McGhee, Charles N J, Cowan, Chad A, Davidson, Alan J, Holm, Teresa M, Sherwin, Trevor
Format: Article
Language:English
Subjects:
Biology and Life Sciences
Cadavers
Cell Culture Techniques
Cell Differentiation
Cell Line
Collagen
Collagen - metabolism
Cornea
Corneal Keratocytes - cytology
Corneal Keratocytes - metabolism
Corneal transplantation
Embryos
Eye diseases
Gene expression
Genotype & phenotype
Human populations
Humans
Immunology
Induced Pluripotent Stem Cells - cytology
Iris - cytology
Keratoconus
Medical treatment
Medicine and Health Sciences
Molecular biology
Neural crest
Neural Crest - cytology
Phenotype
Pluripotency
Research and Analysis Methods
Stem cell transplantation
Stem cells
Stroma
Transplantation
Transplants & implants
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0165464